diff --git a/papers/_posts/2007-07-20-clark-common-sequence-polymorphisms.md b/papers/_posts/2007-07-20-clark-common-sequence-polymorphisms.md new file mode 100644 index 00000000..799cea9a --- /dev/null +++ b/papers/_posts/2007-07-20-clark-common-sequence-polymorphisms.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Common sequence polymorphisms shaping genetic diversity in Arabidopsis thaliana" +nickname: 2007-07-20-clark-common-sequence-polymorphisms +authors: "Clark RM, Schweikert G, Toomajian C, Ossowski S, Zeller G, Shinn P, Warthmann N, Hu TT, Fu G, Hinds DA, Chen H, Frazer KA, Huson DH, Scholkopf B, Nordborg M, Ratsch G, Ecker JR, Weigel D" +year: "2007" +journal: "Science" +volume: 317 +issue: 5836 +pages: 338-42 +is_published: true +image: /assets/images/papers/science.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1126/science.1138632" +pmid: 17641193 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The genomes of individuals from the same species vary in sequence as a result of different evolutionary processes. To examine the patterns of, and the forces shaping, sequence variation in Arabidopsis thaliana, we performed high-density array resequencing of 20 diverse strains (accessions). More than 1 million nonredundant single-nucleotide polymorphisms (SNPs) were identified at moderate false discovery rates (FDRs), and approximately 4% of the genome was identified as being highly dissimilar or deleted relative to the reference genome sequence. Patterns of polymorphism are highly nonrandom among gene families, with genes mediating interaction with the biotic environment having exceptional polymorphism levels. At the chromosomal scale, regional variation in polymorphism was readily apparent. A scan for recent selective sweeps revealed several candidate regions, including a notable example in which almost all variation was removed in a 500-kilobase window. Analyzing the polymorphisms we describe in larger sets of accessions will enable a detailed understanding of forces shaping population-wide sequence variation in A. thaliana. diff --git a/papers/_posts/2008-01-22-laubinger-attax-a-whole.md b/papers/_posts/2008-01-22-laubinger-attax-a-whole.md new file mode 100644 index 00000000..47c20137 --- /dev/null +++ b/papers/_posts/2008-01-22-laubinger-attax-a-whole.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "At-TAX: a whole genome tiling array resource for developmental expression analysis and transcript identification in Arabidopsis thaliana" +nickname: 2008-01-22-laubinger-attax-a-whole +authors: "Laubinger S, Zeller G, Henz SR, Sachsenberg T, Widmer CK, Naouar N, Vuylsteke M, Scholkopf B, Ratsch G, Weigel D" +year: "2008" +journal: "Genome Biol" +volume: 9 +issue: 7 +pages: R112 +is_published: true +image: /assets/images/papers/genome-biol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2530869 +preprint: +supplement: + +# Links +doi: "10.1186/gb-2008-9-7-r112" +pmid: 18613972 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Gene expression maps for model organisms, including Arabidopsis thaliana, have typically been created using gene-centric expression arrays. Here, we describe a comprehensive expression atlas, Arabidopsis thaliana Tiling Array Express (At-TAX), which is based on whole-genome tiling arrays. We demonstrate that tiling arrays are accurate tools for gene expression analysis and identified more than 1,000 unannotated transcribed regions. Visualizations of gene expression estimates, transcribed regions, and tiling probe measurements are accessible online at the At-TAX homepage. diff --git a/papers/_posts/2008-01-22-zeller-transcript-normalization-and.md b/papers/_posts/2008-01-22-zeller-transcript-normalization-and.md new file mode 100644 index 00000000..d65d80e7 --- /dev/null +++ b/papers/_posts/2008-01-22-zeller-transcript-normalization-and.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Transcript normalization and segmentation of tiling array data" +nickname: 2008-01-22-zeller-transcript-normalization-and +authors: "Zeller G, Henz SR, Laubinger S, Weigel D, Ratsch G" +year: "2008" +journal: "Pac Symp Biocomput" +volume: +issue: +pages: 527-38 +is_published: true +image: /assets/images/papers/pac-symp-biocomput.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "" +pmid: 18229713 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +For the analysis of transcriptional tiling arrays we have developed two methods based on state-of-the-art machine learning algorithms. First, we present a novel transcript normalization technique to alleviate the effect of oligonucleotide probe sequences on hybridization intensity. It is specifically designed to decrease the variability observed for individual probes complementary to the same transcript. Applying this normalization technique to Arabidopsis tiling arrays, we are able to reduce sequence biases and also significantly improve separation in signal intensity between exonic and intronic/intergenic probes. Our second contribution is a method for transcript mapping. It extends an algorithm proposed for yeast tiling arrays to the more challenging task of spliced transcript identification. When evaluated on raw versus normalized intensities our method achieves highest prediction accuracy when segmentation is performed on transcript-normalized tiling array data. diff --git a/papers/_posts/2008-06-22-zeller-detecting-polymorphic-regions.md b/papers/_posts/2008-06-22-zeller-detecting-polymorphic-regions.md new file mode 100644 index 00000000..4d915d49 --- /dev/null +++ b/papers/_posts/2008-06-22-zeller-detecting-polymorphic-regions.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Detecting polymorphic regions in Arabidopsis thaliana with resequencing microarrays" +nickname: 2008-06-22-zeller-detecting-polymorphic-regions +authors: "Zeller G, Clark RM, Schneeberger K, Bohlen A, Weigel D, Ratsch G" +year: "2008" +journal: "Genome Res" +volume: 18 +issue: 6 +pages: 918-29 +is_published: true +image: /assets/images/papers/genome-res.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2413159 +preprint: +supplement: + +# Links +doi: "10.1101/gr.070169.107" +pmid: 18323538 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Whole-genome oligonucleotide resequencing arrays have allowed the comprehensive discovery of single nucleotide polymorphisms (SNPs) in eukaryotic genomes of moderate to large size. With this technology, the detection rate for isolated SNPs is typically high. However, it is greatly reduced when other polymorphisms are located near a SNP as multiple mismatches inhibit hybridization to arrayed oligonucleotides. Contiguous tracts of suppressed hybridization therefore typify polymorphic regions (PRs) such as clusters of SNPs or deletions. We developed a machine learning method, designated margin-based prediction of polymorphic regions (mPPR), to predict PRs from resequencing array data. Conceptually similar to hidden Markov models, the method is trained with discriminative learning techniques related to support vector machines, and accurately identifies even very short polymorphic tracts (<10 bp). We applied this method to resequencing array data previously generated for the euchromatic genomes of 20 strains (accessions) of the best-characterized plant, Arabidopsis thaliana. Nonredundantly, 27% of the genome was included within the boundaries of PRs predicted at high specificity ( approximately 97%). The resulting data set provides a fine-scale view of polymorphic sequences in A. thaliana; patterns of polymorphism not apparent in SNP data were readily detected, especially for noncoding regions. Our predictions provide a valuable resource for evolutionary genetic and functional studies in A. thaliana, and our method is applicable to similar data sets in other species. More broadly, our computational approach can be applied to other segmentation tasks related to the analysis of genomic variation. diff --git a/papers/_posts/2008-06-24-laubinger-dual-roles-of.md b/papers/_posts/2008-06-24-laubinger-dual-roles-of.md new file mode 100644 index 00000000..b8fb18e5 --- /dev/null +++ b/papers/_posts/2008-06-24-laubinger-dual-roles-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Dual roles of the nuclear cap-binding complex and SERRATE in pre-mRNA splicing and microRNA processing in Arabidopsis thaliana" +nickname: 2008-06-24-laubinger-dual-roles-of +authors: "Laubinger S, Sachsenberg T, Zeller G, Busch W, Lohmann JU, Ratsch G, Weigel D" +year: "2008" +journal: "Proc Natl Acad Sci U S A" +volume: 105 +issue: 25 +pages: 8795-800 +is_published: true +image: /assets/images/papers/proc-natl-acad-sci-u-s-a.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2426964 +preprint: +supplement: + +# Links +doi: "10.1073/pnas.0802493105" +pmid: 18550839 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The processing of Arabidopsis thaliana microRNAs (miRNAs) from longer primary transcripts (pri-miRNAs) requires the activity of several proteins, including DICER-LIKE1 (DCL1), the double-stranded RNA-binding protein HYPONASTIC LEAVES1 (HYL1), and the zinc finger protein SERRATE (SE). It has been noted before that the morphological appearance of weak se mutants is reminiscent of plants with mutations in ABH1/CBP80 and CBP20, which encode the two subunits of the nuclear cap-binding complex. We report that, like SE, the cap-binding complex is necessary for proper processing of pri-miRNAs. Inactivation of either ABH1/CBP80 or CBP20 results in decreased levels of mature miRNAs accompanied by apparent stabilization of pri-miRNAs. Whole-genome tiling array analyses reveal that se, abh1/cbp80, and cbp20 mutants also share similar splicing defects, leading to the accumulation of many partially spliced transcripts. This is unlikely to be an indirect consequence of improper miRNA processing or other mRNA turnover pathways, because introns retained in se, abh1/cbp80, and cbp20 mutants are not affected by mutations in other genes required for miRNA processing or for nonsense-mediated mRNA decay. Taken together, our results uncover dual roles in splicing and miRNA processing that distinguish SE and the cap-binding complex from specialized miRNA processing factors such as DCL1 and HYL1. diff --git a/papers/_posts/2009-01-22-naouar-quantitative-rna-expression.md b/papers/_posts/2009-01-22-naouar-quantitative-rna-expression.md new file mode 100644 index 00000000..b6e2c77a --- /dev/null +++ b/papers/_posts/2009-01-22-naouar-quantitative-rna-expression.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Quantitative RNA expression analysis with Affymetrix Tiling 1.0R arrays identifies new E2F target genes" +nickname: 2009-01-22-naouar-quantitative-rna-expression +authors: "Naouar N, Vandepoele K, Lammens T, Casneuf T, Zeller G, van Hummelen P, Weigel D, Ratsch G, Inze D, Kuiper M, De Veylder L, Vuylsteke M" +year: "2009" +journal: "Plant J" +volume: 57 +issue: 1 +pages: 184-94 +is_published: true +image: /assets/images/papers/plant-j.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1111/j.1365-313X.2008.03662.x" +pmid: 18764924 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The Affymetrix ATH1 array provides a robust standard tool for transcriptome analysis, but unfortunately does not represent all of the transcribed genes in Arabidopsis thaliana. Recently, Affymetrix has introduced its Arabidopsis Tiling 1.0R array, which offers whole-genome coverage of the sequenced Col-0 reference strain. Here, we present an approach to exploit this platform for quantitative mRNA expression analysis, and compare the results with those obtained using ATH1 arrays. We also propose a method for selecting unique tiling probes for each annotated gene or transcript in the most current genome annotation, TAIR7, generating Chip Definition Files for the Tiling 1.0R array. As a test case, we compared the transcriptome of wild-type plants with that of transgenic plants overproducing the heterodimeric E2Fa-DPa transcription factor. We show that with the appropriate data pre-processing, the estimated changes per gene for those with significantly different expression levels is very similar for the two array types. With the tiling arrays we could identify 368 new E2F-regulated genes, with a large fraction including an E2F motif in the promoter. The latter groups increase the number of excellent candidates for new, direct E2F targets by almost twofold, from 181 to 334. diff --git a/papers/_posts/2009-01-22-plantegenet-comprehensive-analysis-of.md b/papers/_posts/2009-01-22-plantegenet-comprehensive-analysis-of.md new file mode 100644 index 00000000..376f4810 --- /dev/null +++ b/papers/_posts/2009-01-22-plantegenet-comprehensive-analysis-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Comprehensive analysis of Arabidopsis expression level polymorphisms with simple inheritance" +nickname: 2009-01-22-plantegenet-comprehensive-analysis-of +authors: "Plantegenet S, Weber J, Goldstein DR, Zeller G, Nussbaumer C, Thomas J, Weigel D, Harshman K, Hardtke CS" +year: "2009" +journal: "Mol Syst Biol" +volume: 5 +issue: +pages: 242 +is_published: true +image: /assets/images/papers/mol-syst-biol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2657532 +preprint: +supplement: + +# Links +doi: "10.1038/msb.2008.79" +pmid: 19225455 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +In Arabidopsis thaliana, gene expression level polymorphisms (ELPs) between natural accessions that exhibit simple, single locus inheritance are promising quantitative trait locus (QTL) candidates to explain phenotypic variability. It is assumed that such ELPs overwhelmingly represent regulatory element polymorphisms. However, comprehensive genome-wide analyses linking expression level, regulatory sequence and gene structure variation are missing, preventing definite verification of this assumption. Here, we analyzed ELPs observed between the Eil-0 and Lc-0 accessions. Compared with non-variable controls, 5' regulatory sequence variation in the corresponding genes is indeed increased. However, approximately 42% of all the ELP genes also carry major transcription unit deletions in one parent as revealed by genome tiling arrays, representing a >4-fold enrichment over controls. Within the subset of ELPs with simple inheritance, this proportion is even higher and deletions are generally more severe. Similar results were obtained from analyses of the Bay-0 and Sha accessions, using alternative technical approaches. Collectively, our results suggest that drastic structural changes are a major cause for ELPs with simple inheritance, corroborating experimentally observed indel preponderance in cloned Arabidopsis QTL. diff --git a/papers/_posts/2009-06-22-zeller-stressinduced-changes-in.md b/papers/_posts/2009-06-22-zeller-stressinduced-changes-in.md new file mode 100644 index 00000000..75d03de3 --- /dev/null +++ b/papers/_posts/2009-06-22-zeller-stressinduced-changes-in.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Stress-induced changes in the Arabidopsis thaliana transcriptome analyzed using whole-genome tiling arrays" +nickname: 2009-06-22-zeller-stressinduced-changes-in +authors: "Zeller G, Henz SR, Widmer CK, Sachsenberg T, Ratsch G, Weigel D, Laubinger S" +year: "2009" +journal: "Plant J" +volume: 58 +issue: 6 +pages: 1068-82 +is_published: true +image: /assets/images/papers/plant-j.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1111/j.1365-313X.2009.03835.x" +pmid: 19222804 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The responses of plants to abiotic stresses are accompanied by massive changes in transcriptome composition. To provide a comprehensive view of stress-induced changes in the Arabidopsis thaliana transcriptome, we have used whole-genome tiling arrays to analyze the effects of salt, osmotic, cold and heat stress as well as application of the hormone abscisic acid (ABA), an important mediator of stress responses. Among annotated genes in the reference strain Columbia we have found many stress-responsive genes, including several transcription factor genes as well as pseudogenes and transposons that have been missed in previous analyses with standard expression arrays. In addition, we report hundreds of newly identified, stress-induced transcribed regions. These often overlap with known, annotated genes. The results are accessible through the Arabidopsis thaliana Tiling Array Express (At-TAX) homepage, which provides convenient tools for displaying expression values of annotated genes, as well as visualization of unannotated transcribed regions along each chromosome. diff --git a/papers/_posts/2009-07-22-schweikert-mgeneweb-a-web.md b/papers/_posts/2009-07-22-schweikert-mgeneweb-a-web.md new file mode 100644 index 00000000..66d4648b --- /dev/null +++ b/papers/_posts/2009-07-22-schweikert-mgeneweb-a-web.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "mGene.web: a web service for accurate computational gene finding" +nickname: 2009-07-22-schweikert-mgeneweb-a-web +authors: "Schweikert G, Behr J, Zien A, Zeller G, Ong CS, Sonnenburg S, Ratsch G" +year: "2009" +journal: "Nucleic Acids Res" +volume: 37 +issue: Web Server issue +pages: W312-6 +is_published: true +image: /assets/images/papers/nucleic-acids-res.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2703990 +preprint: +supplement: + +# Links +doi: "10.1093/nar/gkp479" +pmid: 19494180 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +We describe mGene.web, a web service for the genome-wide prediction of protein coding genes from eukaryotic DNA sequences. It offers pre-trained models for the recognition of gene structures including untranslated regions in an increasing number of organisms. With mGene.web, users have the additional possibility to train the system with their own data for other organisms on the push of a button, a functionality that will greatly accelerate the annotation of newly sequenced genomes. The system is built in a highly modular way, such that individual components of the framework, like the promoter prediction tool or the splice site predictor, can be used autonomously. The underlying gene finding system mGene is based on discriminative machine learning techniques and its high accuracy has been demonstrated in an international competition on nematode genomes. mGene.web is available at http://www.mgene.org/web, it is free of charge and can be used for eukaryotic genomes of small to moderate size (several hundred Mbp). diff --git a/papers/_posts/2009-07-28-mcnally-genomewide-snp-variation.md b/papers/_posts/2009-07-28-mcnally-genomewide-snp-variation.md new file mode 100644 index 00000000..1cf5a8da --- /dev/null +++ b/papers/_posts/2009-07-28-mcnally-genomewide-snp-variation.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Genomewide SNP variation reveals relationships among landraces and modern varieties of rice" +nickname: 2009-07-28-mcnally-genomewide-snp-variation +authors: "McNally KL, Childs KL, Bohnert R, Davidson RM, Zhao K, Ulat VJ, Zeller G, Clark RM, Hoen DR, Bureau TE, Stokowski R, Ballinger DG, Frazer KA, Cox DR, Padhukasahasram B, Bustamante CD, Weigel D, Mackill DJ, Bruskiewich RM, Ratsch G, Buell CR, Leung H, Leach JE" +year: "2009" +journal: "Proc Natl Acad Sci U S A" +volume: 106 +issue: 30 +pages: 12273-8 +is_published: true +image: /assets/images/papers/proc-natl-acad-sci-u-s-a.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2718348 +preprint: +supplement: + +# Links +doi: "10.1073/pnas.0900992106" +pmid: 19597147 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Rice, the primary source of dietary calories for half of humanity, is the first crop plant for which a high-quality reference genome sequence from a single variety was produced. We used resequencing microarrays to interrogate 100 Mb of the unique fraction of the reference genome for 20 diverse varieties and landraces that capture the impressive genotypic and phenotypic diversity of domesticated rice. Here, we report the distribution of 160,000 nonredundant SNPs. Introgression patterns of shared SNPs revealed the breeding history and relationships among the 20 varieties; some introgressed regions are associated with agronomic traits that mark major milestones in rice improvement. These comprehensive SNP data provide a foundation for deep exploration of rice diversity and gene-trait relationships and their use for future rice improvement. diff --git a/papers/_posts/2009-11-22-schweikert-mgene-accurate-svmbased.md b/papers/_posts/2009-11-22-schweikert-mgene-accurate-svmbased.md new file mode 100644 index 00000000..59e9d335 --- /dev/null +++ b/papers/_posts/2009-11-22-schweikert-mgene-accurate-svmbased.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "mGene: accurate SVM-based gene finding with an application to nematode genomes" +nickname: 2009-11-22-schweikert-mgene-accurate-svmbased +authors: "Schweikert G, Zien A, Zeller G, Behr J, Dieterich C, Ong CS, Philips P, De Bona F, Hartmann L, Bohlen A, Kruger N, Sonnenburg S, Ratsch G" +year: "2009" +journal: "Genome Res" +volume: 19 +issue: 11 +pages: 2133-43 +is_published: true +image: /assets/images/papers/genome-res.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2775605 +preprint: +supplement: + +# Links +doi: "10.1101/gr.090597.108" +pmid: 19564452 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +We present a highly accurate gene-prediction system for eukaryotic genomes, called mGene. It combines in an unprecedented manner the flexibility of generalized hidden Markov models (gHMMs) with the predictive power of modern machine learning methods, such as Support Vector Machines (SVMs). Its excellent performance was proved in an objective competition based on the genome of the nematode Caenorhabditis elegans. Considering the average of sensitivity and specificity, the developmental version of mGene exhibited the best prediction performance on nucleotide, exon, and transcript level for ab initio and multiple-genome gene-prediction tasks. The fully developed version shows superior performance in 10 out of 12 evaluation criteria compared with the other participating gene finders, including Fgenesh++ and Augustus. An in-depth analysis of mGene's genome-wide predictions revealed that approximately 2200 predicted genes were not contained in the current genome annotation. Testing a subset of 57 of these genes by RT-PCR and sequencing, we confirmed expression for 24 (42%) of them. mGene missed 300 annotated genes, out of which 205 were unconfirmed. RT-PCR testing of 24 of these genes resulted in a success rate of merely 8%. These findings suggest that even the gene catalog of a well-studied organism such as C. elegans can be substantially improved by mGene's predictions. We also provide gene predictions for the four nematodes C. briggsae, C. brenneri, C. japonica, and C. remanei. Comparing the resulting proteomes among these organisms and to the known protein universe, we identified many species-specific gene inventions. In a quality assessment of several available annotations for these genomes, we find that mGene's predictions are most accurate. diff --git a/papers/_posts/2010-02-22-rehrauer-agronomics1-a-new.md b/papers/_posts/2010-02-22-rehrauer-agronomics1-a-new.md new file mode 100644 index 00000000..0a696efa --- /dev/null +++ b/papers/_posts/2010-02-22-rehrauer-agronomics1-a-new.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "AGRONOMICS1: a new resource for Arabidopsis transcriptome profiling" +nickname: 2010-02-22-rehrauer-agronomics1-a-new +authors: "Rehrauer H, Aquino C, Gruissem W, Henz SR, Hilson P, Laubinger S, Naouar N, Patrignani A, Rombauts S, Shu H, Van de Peer Y, Vuylsteke M, Weigel D, Zeller G, Hennig L" +year: "2010" +journal: "Plant Physiol" +volume: 152 +issue: 2 +pages: 487-99 +is_published: true +image: /assets/images/papers/plant-physiol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2815891 +preprint: +supplement: + +# Links +doi: "10.1104/pp.109.150185" +pmid: 20032078 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Transcriptome profiling has become a routine tool in biology. For Arabidopsis (Arabidopsis thaliana), the Affymetrix ATH1 expression array is most commonly used, but it lacks about one-third of all annotated genes present in the reference strain. An alternative are tiling arrays, but previous designs have not allowed the simultaneous analysis of both strands on a single array. We introduce AGRONOMICS1, a new Affymetrix Arabidopsis microarray that contains the complete paths of both genome strands, with on average one 25mer probe per 35-bp genome sequence window. In addition, the new AGRONOMICS1 array contains all perfect match probes from the original ATH1 array, allowing for seamless integration of the very large existing ATH1 knowledge base. The AGRONOMICS1 array can be used for diverse functional genomics applications such as reliable expression profiling of more than 30,000 genes, detection of alternative splicing, and chromatin immunoprecipitation coupled to microarrays (ChIP-chip). Here, we describe the design of the array and compare its performance with that of the ATH1 array. We find results from both microarrays to be of similar quality, but AGRONOMICS1 arrays yield robust expression information for many more genes, as expected. Analysis of the ATH1 probes on AGRONOMICS1 arrays produces results that closely mirror those of ATH1 arrays. Finally, the AGRONOMICS1 array is shown to be useful for ChIP-chip experiments. We show that heterochromatic H3K9me2 is strongly confined to the gene body of target genes in euchromatic chromosome regions, suggesting that spreading of heterochromatin is limited outside of pericentromeric regions. diff --git a/papers/_posts/2010-10-12-laubinger-global-effects-of.md b/papers/_posts/2010-10-12-laubinger-global-effects-of.md new file mode 100644 index 00000000..fda0c453 --- /dev/null +++ b/papers/_posts/2010-10-12-laubinger-global-effects-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Global effects of the small RNA biogenesis machinery on the Arabidopsis thaliana transcriptome" +nickname: 2010-10-12-laubinger-global-effects-of +authors: "Laubinger S, Zeller G, Henz SR, Buechel S, Sachsenberg T, Wang JW, Ratsch G, Weigel D" +year: "2010" +journal: "Proc Natl Acad Sci U S A" +volume: 107 +issue: 41 +pages: 17466-73 +is_published: true +image: /assets/images/papers/proc-natl-acad-sci-u-s-a.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC2955092 +preprint: +supplement: + +# Links +doi: "10.1073/pnas.1012891107" +pmid: 20870966 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +In Arabidopsis thaliana, four different dicer-like (DCL) proteins have distinct but partially overlapping functions in the biogenesis of microRNAs (miRNAs) and siRNAs from longer, noncoding precursor RNAs. To analyze the impact of different components of the small RNA biogenesis machinery on the transcriptome, we subjected dcl and other mutants impaired in small RNA biogenesis to whole-genome tiling array analysis. We compared both protein-coding genes and noncoding transcripts, including most pri-miRNAs, in two tissues and several stress conditions. Our analysis revealed a surprising number of common targets in dcl1 and dcl2 dcl3 dcl4 triple mutants. Furthermore, our results suggest that the DCL1 is not only involved in miRNA action but also contributes to silencing of a subset of transposons, apparently through an effect on DNA methylation. diff --git a/papers/_posts/2010-12-24-gerstein-integrative-analysis-of.md b/papers/_posts/2010-12-24-gerstein-integrative-analysis-of.md new file mode 100644 index 00000000..461d3b38 --- /dev/null +++ b/papers/_posts/2010-12-24-gerstein-integrative-analysis-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project" +nickname: 2010-12-24-gerstein-integrative-analysis-of +authors: "Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dose AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska-Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM 3rd, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, Ratsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH" +year: "2010" +journal: "Science" +volume: 330 +issue: 6012 +pages: 1775-87 +is_published: true +image: /assets/images/papers/science.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3142569 +preprint: +supplement: + +# Links +doi: "10.1126/science.1196914" +pmid: 21177976 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome. diff --git a/papers/_posts/2011-01-04-hallem-receptortype-guanylate-cyclase.md b/papers/_posts/2011-01-04-hallem-receptortype-guanylate-cyclase.md new file mode 100644 index 00000000..974571b5 --- /dev/null +++ b/papers/_posts/2011-01-04-hallem-receptortype-guanylate-cyclase.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans" +nickname: 2011-01-04-hallem-receptortype-guanylate-cyclase +authors: "Hallem EA, Spencer WC, McWhirter RD, Zeller G, Henz SR, Ratsch G, Miller DM 3rd, Horvitz HR, Sternberg PW, Ringstad N" +year: "2011" +journal: "Proc Natl Acad Sci U S A" +volume: 108 +issue: 1 +pages: 254-9 +is_published: true +image: /assets/images/papers/proc-natl-acad-sci-u-s-a.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3017194 +preprint: +supplement: + +# Links +doi: "10.1073/pnas.1017354108" +pmid: 21173231 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +CO(2) is both a critical regulator of animal physiology and an important sensory cue for many animals for host detection, food location, and mate finding. The free-living soil nematode Caenorhabditis elegans shows CO(2) avoidance behavior, which requires a pair of ciliated sensory neurons, the BAG neurons. Using in vivo calcium imaging, we show that CO(2) specifically activates the BAG neurons and that the CO(2)-sensing function of BAG neurons requires TAX-2/TAX-4 cyclic nucleotide-gated ion channels and the receptor-type guanylate cyclase GCY-9. Our results delineate a molecular pathway for CO(2) sensing and suggest that activation of a receptor-type guanylate cyclase is an evolutionarily conserved mechanism by which animals detect environmental CO(2). diff --git a/papers/_posts/2011-01-22-brouwers-network-neighbors-of.md b/papers/_posts/2011-01-22-brouwers-network-neighbors-of.md new file mode 100644 index 00000000..be7a3b66 --- /dev/null +++ b/papers/_posts/2011-01-22-brouwers-network-neighbors-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Network neighbors of drug targets contribute to drug side-effect similarity" +nickname: 2011-01-22-brouwers-network-neighbors-of +authors: "Brouwers L, Iskar M, Zeller G, van Noort V, Bork P" +year: "2011" +journal: "PLoS One" +volume: 6 +issue: 7 +pages: e22187 +is_published: true +image: /assets/images/papers/plos-one.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3135612 +preprint: +supplement: + +# Links +doi: "10.1371/journal.pone.0022187" +pmid: 21765950 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +In pharmacology, it is essential to identify the molecular mechanisms of drug action in order to understand adverse side effects. These adverse side effects have been used to infer whether two drugs share a target protein. However, side-effect similarity of drugs could also be caused by their target proteins being close in a molecular network, which as such could cause similar downstream effects. In this study, we investigated the proportion of side-effect similarities that is due to targets that are close in the network compared to shared drug targets. We found that only a minor fraction of side-effect similarities (5.8 %) are caused by drugs targeting proteins close in the network, compared to side-effect similarities caused by overlapping drug targets (64%). Moreover, these targets that cause similar side effects are more often in a linear part of the network, having two or less interactions, than drug targets in general. Based on the examples, we gained novel insight into the molecular mechanisms of side effects associated with several drug targets. Looking forward, such analyses will be extremely useful in the process of drug development to better understand adverse side effects. diff --git a/papers/_posts/2011-02-16-eichner-support-vector-machinesbased.md b/papers/_posts/2011-02-16-eichner-support-vector-machinesbased.md new file mode 100644 index 00000000..dff27805 --- /dev/null +++ b/papers/_posts/2011-02-16-eichner-support-vector-machinesbased.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Support vector machines-based identification of alternative splicing in Arabidopsis thaliana from whole-genome tiling arrays" +nickname: 2011-02-16-eichner-support-vector-machinesbased +authors: "Eichner J, Zeller G, Laubinger S, Ratsch G" +year: "2011" +journal: "BMC Bioinformatics" +volume: 12 +issue: +pages: 55 +is_published: true +image: /assets/images/papers/bmc-bioinformatics.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3051901 +preprint: +supplement: + +# Links +doi: "10.1186/1471-2105-12-55" +pmid: 21324185 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +BACKGROUND: Alternative splicing (AS) is a process which generates several distinct mRNA isoforms from the same gene by splicing different portions out of the precursor transcript. Due to the (patho-)physiological importance of AS, a complete inventory of AS is of great interest. While this is in reach for human and mammalian model organisms, our knowledge of AS in plants has remained more incomplete. Experimental approaches for monitoring AS are either based on transcript sequencing or rely on hybridization to DNA microarrays. Among the microarray platforms facilitating the discovery of AS events, tiling arrays are well-suited for identifying intron retention, the most prevalent type of AS in plants. However, analyzing tiling array data is challenging, because of high noise levels and limited probe coverage. RESULTS: In this work, we present a novel method to detect intron retentions (IR) and exon skips (ES) from tiling arrays. While statistical tests have typically been proposed for this purpose, our method instead utilizes support vector machines (SVMs) which are appreciated for their accuracy and robustness to noise. Existing EST and cDNA sequences served for supervised training and evaluation. Analyzing a large collection of publicly available microarray and sequence data for the model plant A. thaliana, we demonstrated that our method is more accurate than existing approaches. The method was applied in a genome-wide screen which resulted in the discovery of 1,355 IR events. A comparison of these IR events to the TAIR annotation and a large set of short-read RNA-seq data showed that 830 of the predicted IR events are novel and that 525 events (39%) overlap with either the TAIR annotation or the IR events inferred from the RNA-seq data. CONCLUSIONS: The method developed in this work expands the scarce repertoire of analysis tools for the identification of alternative mRNA splicing from whole-genome tiling arrays. Our predictions are highly enriched with known AS events and complement the A. thaliana genome annotation with respect to AS. Since all predicted AS events can be precisely attributed to experimental conditions, our work provides a basis for follow-up studies focused on the elucidation of the regulatory mechanisms underlying tissue-specific and stress-dependent AS in plants. diff --git a/papers/_posts/2011-02-22-spencer-a-spatial-and.md b/papers/_posts/2011-02-22-spencer-a-spatial-and.md new file mode 100644 index 00000000..8946fd12 --- /dev/null +++ b/papers/_posts/2011-02-22-spencer-a-spatial-and.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "A spatial and temporal map of C. elegans gene expression" +nickname: 2011-02-22-spencer-a-spatial-and +authors: "Spencer WC, Zeller G, Watson JD, Henz SR, Watkins KL, McWhirter RD, Petersen S, Sreedharan VT, Widmer C, Jo J, Reinke V, Petrella L, Strome S, Von Stetina SE, Katz M, Shaham S, Ratsch G, Miller DM 3rd" +year: "2011" +journal: "Genome Res" +volume: 21 +issue: 2 +pages: 325-41 +is_published: true +image: /assets/images/papers/genome-res.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3032935 +preprint: +supplement: + +# Links +doi: "10.1101/gr.114595.110" +pmid: 21177967 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The C. elegans genome has been completely sequenced, and the developmental anatomy of this model organism is described at single-cell resolution. Here we utilize strategies that exploit this precisely defined architecture to link gene expression to cell type. We obtained RNAs from specific cells and from each developmental stage using tissue-specific promoters to mark cells for isolation by FACS or for mRNA extraction by the mRNA-tagging method. We then generated gene expression profiles of more than 30 different cells and developmental stages using tiling arrays. Machine-learning-based analysis detected transcripts corresponding to established gene models and revealed novel transcriptionally active regions (TARs) in noncoding domains that comprise at least 10% of the total C. elegans genome. Our results show that about 75% of transcripts with detectable expression are differentially expressed among developmental stages and across cell types. Examination of known tissue- and cell-specific transcripts validates these data sets and suggests that newly identified TARs may exercise cell-specific functions. Additionally, we used self-organizing maps to define groups of coregulated transcripts and applied regulatory element analysis to identify known transcription factor- and miRNA-binding sites, as well as novel motifs that likely function to control subsets of these genes. By using cell-specific, whole-genome profiling strategies, we have detected a large number of novel transcripts and produced high-resolution gene expression maps that provide a basis for establishing the roles of individual genes in cellular differentiation. diff --git a/papers/_posts/2011-05-12-arumugam-enterotypes-of-the.md b/papers/_posts/2011-05-12-arumugam-enterotypes-of-the.md new file mode 100644 index 00000000..5e2c40ca --- /dev/null +++ b/papers/_posts/2011-05-12-arumugam-enterotypes-of-the.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Enterotypes of the human gut microbiome" +nickname: 2011-05-12-arumugam-enterotypes-of-the +authors: "Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Dore J, Antolin M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Merieux A, Melo Minardi R, M'rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P" +year: "2011" +journal: "Nature" +volume: 473 +issue: 7346 +pages: 174-80 +is_published: true +image: /assets/images/papers/nature.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3728647 +preprint: +supplement: + +# Links +doi: "10.1038/nature09944" +pmid: 21508958 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers. diff --git a/papers/_posts/2011-12-22-zhao-prediction-of-drug.md b/papers/_posts/2011-12-22-zhao-prediction-of-drug.md new file mode 100644 index 00000000..e57fdf55 --- /dev/null +++ b/papers/_posts/2011-12-22-zhao-prediction-of-drug.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Prediction of drug combinations by integrating molecular and pharmacological data" +nickname: 2011-12-22-zhao-prediction-of-drug +authors: "Zhao XM, Iskar M, Zeller G, Kuhn M, van Noort V, Bork P" +year: "2011" +journal: "PLoS Comput Biol" +volume: 7 +issue: 12 +pages: e1002323 +is_published: true +image: /assets/images/papers/plos-comput-biol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3248384 +preprint: +supplement: + +# Links +doi: "10.1371/journal.pcbi.1002323" +pmid: 22219721 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Combinatorial therapy is a promising strategy for combating complex disorders due to improved efficacy and reduced side effects. However, screening new drug combinations exhaustively is impractical considering all possible combinations between drugs. Here, we present a novel computational approach to predict drug combinations by integrating molecular and pharmacological data. Specifically, drugs are represented by a set of their properties, such as their targets or indications. By integrating several of these features, we show that feature patterns enriched in approved drug combinations are not only predictive for new drug combinations but also provide insights into mechanisms underlying combinatorial therapy. Further analysis confirmed that among our top ranked predictions of effective combinations, 69% are supported by literature, while the others represent novel potential drug combinations. We believe that our proposed approach can help to limit the search space of drug combinations and provide a new way to effectively utilize existing drugs for new purposes. diff --git a/papers/_posts/2012-08-22-iskar-drug-discovery-in.md b/papers/_posts/2012-08-22-iskar-drug-discovery-in.md new file mode 100644 index 00000000..da7a89f6 --- /dev/null +++ b/papers/_posts/2012-08-22-iskar-drug-discovery-in.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Drug discovery in the age of systems biology: the rise of computational approaches for data integration" +nickname: 2012-08-22-iskar-drug-discovery-in +authors: "Iskar M, Zeller G, Zhao XM, van Noort V, Bork P" +year: "2012" +journal: "Curr Opin Biotechnol" +volume: 23 +issue: 4 +pages: 609-16 +is_published: true +image: /assets/images/papers/curr-opin-biotechnol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1016/j.copbio.2011.11.010" +pmid: 22153034 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The increased availability of large-scale open-access resources on bioactivities of small molecules has a significant impact on pharmacology facilitated mainly by computational approaches that digest the vast amounts of data. We discuss here how computational data integration enables systemic views on a drug's action and allows to tackle complex problems such as the large-scale prediction of drug targets, drug repurposing, the molecular mechanisms, cellular responses or side effects. We particularly focus on computational methods that leverage various cell-based transcriptional, proteomic and phenotypic profiles of drug response in order to gain a systemic view of drug action at the molecular, cellular and whole-organism scale. diff --git a/papers/_posts/2013-01-22-iskar-characterization-of-druginduced.md b/papers/_posts/2013-01-22-iskar-characterization-of-druginduced.md new file mode 100644 index 00000000..1beee2ec --- /dev/null +++ b/papers/_posts/2013-01-22-iskar-characterization-of-druginduced.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Characterization of drug-induced transcriptional modules: towards drug repositioning and functional understanding" +nickname: 2013-01-22-iskar-characterization-of-druginduced +authors: "Iskar M, Zeller G, Blattmann P, Campillos M, Kuhn M, Kaminska KH, Runz H, Gavin AC, Pepperkok R, van Noort V, Bork P" +year: "2013" +journal: "Mol Syst Biol" +volume: 9 +issue: +pages: 662 +is_published: true +image: /assets/images/papers/mol-syst-biol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3658274 +preprint: +supplement: + +# Links +doi: "10.1038/msb.2013.20" +pmid: 23632384 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +In pharmacology, it is crucial to understand the complex biological responses that drugs elicit in the human organism and how well they can be inferred from model organisms. We therefore identified a large set of drug-induced transcriptional modules from genome-wide microarray data of drug-treated human cell lines and rat liver, and first characterized their conservation. Over 70% of these modules were common for multiple cell lines and 15% were conserved between the human in vitro and the rat in vivo system. We then illustrate the utility of conserved and cell-type-specific drug-induced modules by predicting and experimentally validating (i) gene functions, e.g., 10 novel regulators of cellular cholesterol homeostasis and (ii) new mechanisms of action for existing drugs, thereby providing a starting point for drug repositioning, e.g., novel cell cycle inhibitors and new modulators of alpha-adrenergic receptor, peroxisome proliferator-activated receptor and estrogen receptor. Taken together, the identified modules reveal the conservation of transcriptional responses towards drugs across cell types and organisms, and improve our understanding of both the molecular basis of drug action and human biology. diff --git a/papers/_posts/2013-09-22-mende-accurate-and-universal.md b/papers/_posts/2013-09-22-mende-accurate-and-universal.md new file mode 100644 index 00000000..6715a88b --- /dev/null +++ b/papers/_posts/2013-09-22-mende-accurate-and-universal.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Accurate and universal delineation of prokaryotic species" +nickname: 2013-09-22-mende-accurate-and-universal +authors: "Mende DR, Sunagawa S, Zeller G, Bork P" +year: "2013" +journal: "Nat Methods" +volume: 10 +issue: 9 +pages: 881-4 +is_published: true +image: /assets/images/papers/nat-methods.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1038/nmeth.2575" +pmid: 23892899 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The exponentially increasing number of sequenced genomes necessitates fast, accurate, universally applicable and automated approaches for the delineation of prokaryotic species. We developed specI (species identification tool; http://www.bork.embl.de/software/specI/), a method to group organisms into species clusters based on 40 universal, single-copy phylogenetic marker genes. Applied to 3,496 prokaryotic genomes, specI identified 1,753 species clusters. Of 314 discrepancies with a widely used taxonomic classification, >62% were resolved by literature support. diff --git a/papers/_posts/2013-12-22-sunagawa-metagenomic-species-profiling.md b/papers/_posts/2013-12-22-sunagawa-metagenomic-species-profiling.md new file mode 100644 index 00000000..bcb35e46 --- /dev/null +++ b/papers/_posts/2013-12-22-sunagawa-metagenomic-species-profiling.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Metagenomic species profiling using universal phylogenetic marker genes" +nickname: 2013-12-22-sunagawa-metagenomic-species-profiling +authors: "Sunagawa S, Mende DR, Zeller G, Izquierdo-Carrasco F, Berger SA, Kultima JR, Coelho LP, Arumugam M, Tap J, Nielsen HB, Rasmussen S, Brunak S, Pedersen O, Guarner F, de Vos WM, Wang J, Li J, Dore J, Ehrlich SD, Stamatakis A, Bork P" +year: "2013" +journal: "Nat Methods" +volume: 10 +issue: 12 +pages: 1196-9 +is_published: true +image: /assets/images/papers/nat-methods.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1038/nmeth.2693" +pmid: 24141494 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +To quantify known and unknown microorganisms at species-level resolution using shotgun sequencing data, we developed a method that establishes metagenomic operational taxonomic units (mOTUs) based on single-copy phylogenetic marker genes. Applied to 252 human fecal samples, the method revealed that on average 43% of the species abundance and 58% of the richness cannot be captured by current reference genome-based methods. An implementation of the method is available at http://www.bork.embl.de/software/mOTU/. diff --git a/papers/_posts/2014-05-01-sreedharan-oqtans-the-rnaseq.md b/papers/_posts/2014-05-01-sreedharan-oqtans-the-rnaseq.md new file mode 100644 index 00000000..8ba68b0a --- /dev/null +++ b/papers/_posts/2014-05-01-sreedharan-oqtans-the-rnaseq.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Oqtans: the RNA-seq workbench in the cloud for complete and reproducible quantitative transcriptome analysis" +nickname: 2014-05-01-sreedharan-oqtans-the-rnaseq +authors: "Sreedharan VT, Schultheiss SJ, Jean G, Kahles A, Bohnert R, Drewe P, Mudrakarta P, Gornitz N, Zeller G, Ratsch G" +year: "2014" +journal: "Bioinformatics" +volume: 30 +issue: 9 +pages: 1300-1 +is_published: true +image: /assets/images/papers/bioinformatics.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC3998122 +preprint: +supplement: + +# Links +doi: "10.1093/bioinformatics/btt731" +pmid: 24413671 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +We present Oqtans, an open-source workbench for quantitative transcriptome analysis, that is integrated in Galaxy. Its distinguishing features include customizable computational workflows and a modular pipeline architecture that facilitates comparative assessment of tool and data quality. Oqtans integrates an assortment of machine learning-powered tools into Galaxy, which show superior or equal performance to state-of-the-art tools. Implemented tools comprise a complete transcriptome analysis workflow: short-read alignment, transcript identification/quantification and differential expression analysis. Oqtans and Galaxy facilitate persistent storage, data exchange and documentation of intermediate results and analysis workflows. We illustrate how Oqtans aids the interpretation of data from different experiments in easy to understand use cases. Users can easily create their own workflows and extend Oqtans by integrating specific tools. Oqtans is available as (i) a cloud machine image with a demo instance at cloud.oqtans.org, (ii) a public Galaxy instance at galaxy.cbio.mskcc.org, (iii) a git repository containing all installed software (oqtans.org/git); most of which is also available from (iv) the Galaxy Toolshed and (v) a share string to use along with Galaxy CloudMan. diff --git a/papers/_posts/2014-10-15-van-novel-drug-candidates.md b/papers/_posts/2014-10-15-van-novel-drug-candidates.md new file mode 100644 index 00000000..5235e37e --- /dev/null +++ b/papers/_posts/2014-10-15-van-novel-drug-candidates.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Novel drug candidates for the treatment of metastatic colorectal cancer through global inverse gene-expression profiling" +nickname: 2014-10-15-van-novel-drug-candidates +authors: "van Noort V, Scholch S, Iskar M, Zeller G, Ostertag K, Schweitzer C, Werner K, Weitz J, Koch M, Bork P" +year: "2014" +journal: "Cancer Res" +volume: 74 +issue: 20 +pages: 5690-9 +is_published: true +image: /assets/images/papers/cancer-res.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1158/0008-5472.CAN-13-3540" +pmid: 25038229 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Drug-induced gene-expression profiles that invert disease profiles have recently been illustrated to be a starting point for drug repositioning. In this study, we validate this approach and focus on prediction of novel drugs for colorectal cancer, for which there is a pressing need to find novel antimetastatic compounds. We computationally predicted three novel and still unknown compounds against colorectal cancer: citalopram (an antidepressant), troglitazone (an antidiabetic), and enilconazole (a fungicide). We verified the compounds by in vitro assays of clonogenic survival, proliferation, and migration and in a subcutaneous mouse model. We found evidence that the mode of action of these compounds may be through inhibition of TGFbeta signaling. Furthermore, one compound, citalopram, reduced tumor size as well as the number of circulating tumor cells and metastases in an orthotopic mouse model of colorectal cancer. This study proposes citalopram as a potential therapeutic option for patients with colorectal cancer, illustrating the potential of systems pharmacology. diff --git a/papers/_posts/2014-11-28-zeller-potential-of-fecal.md b/papers/_posts/2014-11-28-zeller-potential-of-fecal.md new file mode 100644 index 00000000..8fb31fc2 --- /dev/null +++ b/papers/_posts/2014-11-28-zeller-potential-of-fecal.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Potential of fecal microbiota for early-stage detection of colorectal cancer" +nickname: 2014-11-28-zeller-potential-of-fecal +authors: "Zeller G, Tap J, Voigt AY, Sunagawa S, Kultima JR, Costea PI, Amiot A, Bohm J, Brunetti F, Habermann N, Hercog R, Koch M, Luciani A, Mende DR, Schneider MA, Schrotz-King P, Tournigand C, Tran Van Nhieu J, Yamada T, Zimmermann J, Benes V, Kloor M, Ulrich CM, von Knebel Doeberitz M, Sobhani I, Bork P" +year: "2014" +journal: "Mol Syst Biol" +volume: 10 +issue: 11 +pages: 766 +is_published: true +image: /assets/images/papers/mol-syst-biol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC4299606 +preprint: +supplement: + +# Links +doi: "10.15252/msb.20145645" +pmid: 25432777 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism. diff --git a/papers/_posts/2015-04-08-voigt-temporal-and-technical.md b/papers/_posts/2015-04-08-voigt-temporal-and-technical.md new file mode 100644 index 00000000..ba646406 --- /dev/null +++ b/papers/_posts/2015-04-08-voigt-temporal-and-technical.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Temporal and technical variability of human gut metagenomes" +nickname: 2015-04-08-voigt-temporal-and-technical +authors: "Voigt AY, Costea PI, Kultima JR, Li SS, Zeller G, Sunagawa S, Bork P" +year: "2015" +journal: "Genome Biol" +volume: 16 +issue: 1 +pages: 73 +is_published: true +image: /assets/images/papers/genome-biol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC4416267 +preprint: +supplement: + +# Links +doi: "10.1186/s13059-015-0639-8" +pmid: 25888008 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +BACKGROUND: Metagenomics has become a prominent approach for exploring the role of the gut microbiota in human health. However, the temporal variability of the healthy gut microbiome has not yet been studied in depth using metagenomics and little is known about the effects of different sampling and preservation approaches. We performed metagenomic analysis on fecal samples from seven subjects collected over a period of up to two years to investigate temporal variability and assess preservation-induced variation, specifically, fresh frozen compared to RNALater. We also monitored short-term disturbances caused by antibiotic treatment and bowel cleansing in one subject. RESULTS: We find that the human gut microbiome is temporally stable and highly personalized at both taxonomic and functional levels. Over multiple time points, samples from the same subject clustered together, even in the context of a large dataset of 888 European and American fecal metagenomes. One exception was observed in an antibiotic intervention case where, more than one year after the treatment, samples did not resemble the pre-treatment state. Clustering was not affected by the preservation method. No species differed significantly in abundance, and only 0.36% of gene families were differentially abundant between preservation methods. CONCLUSIONS: Technical variability is small compared to the temporal variability of an unperturbed gut microbiome, which in turn is much smaller than the observed between-subject variability. Thus, short-term preservation of fecal samples in RNALater is an appropriate and cost-effective alternative to freezing of fecal samples for metagenomic studies. diff --git a/papers/_posts/2015-05-22-sunagawa-ocean-plankton-structure.md b/papers/_posts/2015-05-22-sunagawa-ocean-plankton-structure.md new file mode 100644 index 00000000..8d4478e8 --- /dev/null +++ b/papers/_posts/2015-05-22-sunagawa-ocean-plankton-structure.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Ocean plankton. Structure and function of the global ocean microbiome" +nickname: 2015-05-22-sunagawa-ocean-plankton-structure +authors: "Sunagawa S, Coelho LP, Chaffron S, Kultima JR, Labadie K, Salazar G, Djahanschiri B, Zeller G, Mende DR, Alberti A, Cornejo-Castillo FM, Costea PI, Cruaud C, d'Ovidio F, Engelen S, Ferrera I, Gasol JM, Guidi L, Hildebrand F, Kokoszka F, Lepoivre C, Lima-Mendez G, Poulain J, Poulos BT, Royo-Llonch M, Sarmento H, Vieira-Silva S, Dimier C, Picheral M, Searson S, Kandels-Lewis S, Bowler C, de Vargas C, Gorsky G, Grimsley N, Hingamp P, Iudicone D, Jaillon O, Not F, Ogata H, Pesant S, Speich S, Stemmann L, Sullivan MB, Weissenbach J, Wincker P, Karsenti E, Raes J, Acinas SG, Bork P" +year: "2015" +journal: "Science" +volume: 348 +issue: 6237 +pages: 1261359 +is_published: true +image: /assets/images/papers/science.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1126/science.1261359" +pmid: 25999513 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Microbes are dominant drivers of biogeochemical processes, yet drawing a global picture of functional diversity, microbial community structure, and their ecological determinants remains a grand challenge. We analyzed 7.2 terabases of metagenomic data from 243 Tara Oceans samples from 68 locations in epipelagic and mesopelagic waters across the globe to generate an ocean microbial reference gene catalog with >40 million nonredundant, mostly novel sequences from viruses, prokaryotes, and picoeukaryotes. Using 139 prokaryote-enriched samples, containing >35,000 species, we show vertical stratification with epipelagic community composition mostly driven by temperature rather than other environmental factors or geography. We identify ocean microbial core functionality and reveal that >73% of its abundance is shared with the human gut microbiome despite the physicochemical differences between these two ecosystems. diff --git a/papers/_posts/2016-01-22-vogtmann-colorectal-cancer-and.md b/papers/_posts/2016-01-22-vogtmann-colorectal-cancer-and.md new file mode 100644 index 00000000..d09b9c76 --- /dev/null +++ b/papers/_posts/2016-01-22-vogtmann-colorectal-cancer-and.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing" +nickname: 2016-01-22-vogtmann-colorectal-cancer-and +authors: "Vogtmann E, Hua X, Zeller G, Sunagawa S, Voigt AY, Hercog R, Goedert JJ, Shi J, Bork P, Sinha R" +year: "2016" +journal: "PLoS One" +volume: 11 +issue: 5 +pages: e0155362 +is_published: true +image: /assets/images/papers/plos-one.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC4865240 +preprint: +supplement: + +# Links +doi: "10.1371/journal.pone.0155362" +pmid: 27171425 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect associations that are reproducible and significant after correction for multiple testing. diff --git a/papers/_posts/2016-03-22-noguera-julian-gut-microbiota-linked.md b/papers/_posts/2016-03-22-noguera-julian-gut-microbiota-linked.md new file mode 100644 index 00000000..4475bc3a --- /dev/null +++ b/papers/_posts/2016-03-22-noguera-julian-gut-microbiota-linked.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Gut Microbiota Linked to Sexual Preference and HIV Infection" +nickname: 2016-03-22-noguera-julian-gut-microbiota-linked +authors: "Noguera-Julian M, Rocafort M, Guillen Y, Rivera J, Casadella M, Nowak P, Hildebrand F, Zeller G, Parera M, Bellido R, Rodriguez C, Carrillo J, Mothe B, Coll J, Bravo I, Estany C, Herrero C, Saz J, Sirera G, Torrela A, Navarro J, Crespo M, Brander C, Negredo E, Blanco J, Guarner F, Calle ML, Bork P, Sonnerborg A, Clotet B, Paredes R" +year: "2016" +journal: "EBioMedicine" +volume: 5 +issue: +pages: 135-46 +is_published: true +image: /assets/images/papers/ebiomedicine.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC4816837 +preprint: +supplement: + +# Links +doi: "10.1016/j.ebiom.2016.01.032" +pmid: 27077120 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The precise effects of HIV-1 on the gut microbiome are unclear. Initial cross-sectional studies provided contradictory associations between microbial richness and HIV serostatus and suggested shifts from Bacteroides to Prevotella predominance following HIV-1 infection, which have not been found in animal models or in studies matched for HIV-1 transmission groups. In two independent cohorts of HIV-1-infected subjects and HIV-1-negative controls in Barcelona (n = 156) and Stockholm (n = 84), men who have sex with men (MSM) predominantly belonged to the Prevotella-rich enterotype whereas most non-MSM subjects were enriched in Bacteroides, independently of HIV-1 status, and with only a limited contribution of diet effects. Moreover, MSM had a significantly richer and more diverse fecal microbiota than non-MSM individuals. After stratifying for sexual orientation, there was no solid evidence of an HIV-specific dysbiosis. However, HIV-1 infection remained consistently associated with reduced bacterial richness, the lowest bacterial richness being observed in subjects with a virological-immune discordant response to antiretroviral therapy. Our findings indicate that HIV gut microbiome studies must control for HIV risk factors and suggest interventions on gut bacterial richness as possible novel avenues to improve HIV-1-associated immune dysfunction. diff --git a/papers/_posts/2016-04-29-li-durable-coexistence-of.md b/papers/_posts/2016-04-29-li-durable-coexistence-of.md new file mode 100644 index 00000000..5c6a594f --- /dev/null +++ b/papers/_posts/2016-04-29-li-durable-coexistence-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Durable coexistence of donor and recipient strains after fecal microbiota transplantation" +nickname: 2016-04-29-li-durable-coexistence-of +authors: "Li SS, Zhu A, Benes V, Costea PI, Hercog R, Hildebrand F, Huerta-Cepas J, Nieuwdorp M, Salojarvi J, Voigt AY, Zeller G, Sunagawa S, de Vos WM, Bork P" +year: "2016" +journal: "Science" +volume: 352 +issue: 6285 +pages: 586-9 +is_published: true +image: /assets/images/papers/science.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1126/science.aad8852" +pmid: 27126044 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Fecal microbiota transplantation (FMT) has shown efficacy in treating recurrent Clostridium difficile infection and is increasingly being applied to other gastrointestinal disorders, yet the fate of native and introduced microbial strains remains largely unknown. To quantify the extent of donor microbiota colonization, we monitored strain populations in fecal samples from a recent FMT study on metabolic syndrome patients using single-nucleotide variants in metagenomes. We found extensive coexistence of donor and recipient strains, persisting 3 months after treatment. Colonization success was greater for conspecific strains than for new species, the latter falling within fluctuation levels observed in healthy individuals over a similar time frame. Furthermore, same-donor recipients displayed varying degrees of microbiota transfer, indicating individual patterns of microbiome resistance and donor-recipient compatibilities. diff --git a/papers/_posts/2016-08-15-kultima-mocat2-a-metagenomic.md b/papers/_posts/2016-08-15-kultima-mocat2-a-metagenomic.md new file mode 100644 index 00000000..f2135ef1 --- /dev/null +++ b/papers/_posts/2016-08-15-kultima-mocat2-a-metagenomic.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "MOCAT2: a metagenomic assembly, annotation and profiling framework" +nickname: 2016-08-15-kultima-mocat2-a-metagenomic +authors: "Kultima JR, Coelho LP, Forslund K, Huerta-Cepas J, Li SS, Driessen M, Voigt AY, Zeller G, Sunagawa S, Bork P" +year: "2016" +journal: "Bioinformatics" +volume: 32 +issue: 16 +pages: 2520-3 +is_published: true +image: /assets/images/papers/bioinformatics.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC4978931 +preprint: +supplement: + +# Links +doi: "10.1093/bioinformatics/btw183" +pmid: 27153620 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +MOCAT2 is a software pipeline for metagenomic sequence assembly and gene prediction with novel features for taxonomic and functional abundance profiling. The automated generation and efficient annotation of non-redundant reference catalogs by propagating pre-computed assignments from 18 databases covering various functional categories allows for fast and comprehensive functional characterization of metagenomes. AVAILABILITY AND IMPLEMENTATION: MOCAT2 is implemented in Perl 5 and Python 2.7, designed for 64-bit UNIX systems and offers support for high-performance computer usage via LSF, PBS or SGE queuing systems; source code is freely available under the GPL3 license at http://mocat.embl.de CONTACT: : bork@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. diff --git a/papers/_posts/2016-09-15-deghou-carta-chemical-annotation.md b/papers/_posts/2016-09-15-deghou-carta-chemical-annotation.md new file mode 100644 index 00000000..aa12d1e1 --- /dev/null +++ b/papers/_posts/2016-09-15-deghou-carta-chemical-annotation.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "CART-a chemical annotation retrieval toolkit" +nickname: 2016-09-15-deghou-carta-chemical-annotation +authors: "Deghou S, Zeller G, Iskar M, Driessen M, Castillo M, van Noort V, Bork P" +year: "2016" +journal: "Bioinformatics" +volume: 32 +issue: 18 +pages: 2869-71 +is_published: true +image: /assets/images/papers/bioinformatics.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC5018367 +preprint: +supplement: + +# Links +doi: "10.1093/bioinformatics/btw233" +pmid: 27256313 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +MOTIVATION: Data on bioactivities of drug-like chemicals are rapidly accumulating in public repositories, creating new opportunities for research in computational systems pharmacology. However, integrative analysis of these data sets is difficult due to prevailing ambiguity between chemical names and identifiers and a lack of cross-references between databases. RESULTS: To address this challenge, we have developed CART, a Chemical Annotation Retrieval Toolkit. As a key functionality, it matches an input list of chemical names into a comprehensive reference space to assign unambiguous chemical identifiers. In this unified space, bioactivity annotations can be easily retrieved from databases covering a wide variety of chemical effects on biological systems. Subsequently, CART can determine annotations enriched in the input set of chemicals and display these in tabular format and interactive network visualizations, thereby facilitating integrative analysis of chemical bioactivity data. AVAILABILITY AND IMPLEMENTATION: CART is available as a Galaxy web service (cart.embl.de). Source code and an easy-to-install command line tool can also be obtained from the web site. CONTACT: bork@embl.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. diff --git a/papers/_posts/2017-02-22-voigt-microbial-biomarkers-for.md b/papers/_posts/2017-02-22-voigt-microbial-biomarkers-for.md new file mode 100644 index 00000000..f9334425 --- /dev/null +++ b/papers/_posts/2017-02-22-voigt-microbial-biomarkers-for.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "[Microbial Biomarkers for Early Cancer Detection]" +nickname: 2017-02-22-voigt-microbial-biomarkers-for +authors: "Voigt AY, Zeller G, Bork P" +year: "2017" +journal: "Dtsch Med Wochenschr" +volume: 142 +issue: 4 +pages: 267-274 +is_published: true +image: /assets/images/papers/dtsch-med-wochenschr.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1055/s-0042-110193" +pmid: 28235227 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The human microbiome - the vast amount of microbes that colonize our body - play an important role in maintaining our health. Changes in microbiome composition have been linked to multiple diseases including cancer. Although mechanisms and causalities of these associations still have to be uncovered, microbiome alterations across various stages of disease can be utilized for novel diagnostic and prognostic tests. Research on biomarkers extracted from the gut microbiome has in particular focused on colorectal cancer, where clinical use is already on the horizon. For example, multiple microbial taxonomic markers such as Fusobacterium nucleatum and other oral pathogens have been identified in human feces with potential for non-invasive diagnostics and prognostics. The article summarizes the recent developments, but also limitations and challenges for the development of microbiome-based biomarkers for cancer early detection. diff --git a/papers/_posts/2017-11-22-costea-towards-standards-for.md b/papers/_posts/2017-11-22-costea-towards-standards-for.md new file mode 100644 index 00000000..8399b013 --- /dev/null +++ b/papers/_posts/2017-11-22-costea-towards-standards-for.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Towards standards for human fecal sample processing in metagenomic studies" +nickname: 2017-11-22-costea-towards-standards-for +authors: "Costea PI, Zeller G, Sunagawa S, Pelletier E, Alberti A, Levenez F, Tramontano M, Driessen M, Hercog R, Jung FE, Kultima JR, Hayward MR, Coelho LP, Allen-Vercoe E, Bertrand L, Blaut M, Brown JRM, Carton T, Cools-Portier S, Daigneault M, Derrien M, Druesne A, de Vos WM, Finlay BB, Flint HJ, Guarner F, Hattori M, Heilig H, Luna RA, van Hylckama Vlieg J, Junick J, Klymiuk I, Langella P, Le Chatelier E, Mai V, Manichanh C, Martin JC, Mery C, Morita H, O'Toole PW, Orvain C, Patil KR, Penders J, Persson S, Pons N, Popova M, Salonen A, Saulnier D, Scott KP, Singh B, Slezak K, Veiga P, Versalovic J, Zhao L, Zoetendal EG, Ehrlich SD, Dore J, Bork P" +year: "2017" +journal: "Nat Biotechnol" +volume: 35 +issue: 11 +pages: 1069-1076 +is_published: true +image: /assets/images/papers/nat-biotechnol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1038/nbt.3960" +pmid: 28967887 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Technical variation in metagenomic analysis must be minimized to confidently assess the contributions of microbiota to human health. Here we tested 21 representative DNA extraction protocols on the same fecal samples and quantified differences in observed microbial community composition. We compared them with differences due to library preparation and sample storage, which we contrasted with observed biological variation within the same specimen or within an individual over time. We found that DNA extraction had the largest effect on the outcome of metagenomic analysis. To rank DNA extraction protocols, we considered resulting DNA quantity and quality, and we ascertained biases in estimates of community diversity and the ratio between Gram-positive and Gram-negative bacteria. We recommend a standardized DNA extraction method for human fecal samples, for which transferability across labs was established and which was further benchmarked using a mock community of known composition. Its adoption will improve comparability of human gut microbiome studies and facilitate meta-analyses. diff --git a/papers/_posts/2017-12-14-costea-subspecies-in-the.md b/papers/_posts/2017-12-14-costea-subspecies-in-the.md new file mode 100644 index 00000000..a524356b --- /dev/null +++ b/papers/_posts/2017-12-14-costea-subspecies-in-the.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Subspecies in the global human gut microbiome" +nickname: 2017-12-14-costea-subspecies-in-the +authors: "Costea PI, Coelho LP, Sunagawa S, Munch R, Huerta-Cepas J, Forslund K, Hildebrand F, Kushugulova A, Zeller G, Bork P" +year: "2017" +journal: "Mol Syst Biol" +volume: 13 +issue: 12 +pages: 960 +is_published: true +image: /assets/images/papers/mol-syst-biol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC5740502 +preprint: +supplement: + +# Links +doi: "10.15252/msb.20177589" +pmid: 29242367 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large-scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture-independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72% of the total assigned microbial abundance, single-nucleotide variation clearly indicates the existence of sub-populations (here termed subspecies). A single subspecies (per species) usually dominates within each host, as expected from ecological theory. At the global scale, geographic distributions of subspecies differ between phyla, with Firmicutes subspecies being significantly more geographically restricted. To investigate the functional significance of the delineated subspecies, we identified genes that consistently distinguish them in a manner that is independent of reference genomes. We further associated these subspecies-specific genes with properties of the microbial community and the host. For example, two of the three Eubacterium rectale subspecies consistently harbor an accessory pro-inflammatory flagellum operon that is associated with lower gut community diversity, higher host BMI, and higher blood fasting insulin levels. Using an additional 676 human oral samples, we further demonstrate the existence of niche specialized subspecies in the different parts of the oral cavity. Taken together, we provide evidence for subspecies in the majority of abundant gut prokaryotes, leading to a better functional and ecological understanding of the human gut microbiome in conjunction with its host. diff --git a/papers/_posts/2018-01-22-costea-enterotypes-in-the.md b/papers/_posts/2018-01-22-costea-enterotypes-in-the.md new file mode 100644 index 00000000..5e6ddffb --- /dev/null +++ b/papers/_posts/2018-01-22-costea-enterotypes-in-the.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Enterotypes in the landscape of gut microbial community composition" +nickname: 2018-01-22-costea-enterotypes-in-the +authors: "Costea PI, Hildebrand F, Arumugam M, Backhed F, Blaser MJ, Bushman FD, de Vos WM, Ehrlich SD, Fraser CM, Hattori M, Huttenhower C, Jeffery IB, Knights D, Lewis JD, Ley RE, Ochman H, O'Toole PW, Quince C, Relman DA, Shanahan F, Sunagawa S, Wang J, Weinstock GM, Wu GD, Zeller G, Zhao L, Raes J, Knight R, Bork P" +year: "2018" +journal: "Nat Microbiol" +volume: 3 +issue: 1 +pages: 8-16 +is_published: true +image: /assets/images/papers/nat-microbiol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC5832044 +preprint: +supplement: + +# Links +doi: "10.1038/s41564-017-0072-8" +pmid: 29255284 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Population stratification is a useful approach for a better understanding of complex biological problems in human health and wellbeing. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types termed enterotypes, has been met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the concept of enterotypes, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into functional, ecological and medical contexts. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept. diff --git a/papers/_posts/2018-03-29-maier-extensive-impact-of.md b/papers/_posts/2018-03-29-maier-extensive-impact-of.md new file mode 100644 index 00000000..4370a383 --- /dev/null +++ b/papers/_posts/2018-03-29-maier-extensive-impact-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Extensive impact of non-antibiotic drugs on human gut bacteria" +nickname: 2018-03-29-maier-extensive-impact-of +authors: "Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, Brochado AR, Fernandez KC, Dose H, Mori H, Patil KR, Bork P, Typas A" +year: "2018" +journal: "Nature" +volume: 555 +issue: 7698 +pages: 623-628 +is_published: true +image: /assets/images/papers/nature.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC6108420 +preprint: +supplement: + +# Links +doi: "10.1038/nature25979" +pmid: 29555994 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance. diff --git a/papers/_posts/2018-04-22-tramontano-nutritional-preferences-of.md b/papers/_posts/2018-04-22-tramontano-nutritional-preferences-of.md new file mode 100644 index 00000000..dad3dab7 --- /dev/null +++ b/papers/_posts/2018-04-22-tramontano-nutritional-preferences-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies" +nickname: 2018-04-22-tramontano-nutritional-preferences-of +authors: "Tramontano M, Andrejev S, Pruteanu M, Klunemann M, Kuhn M, Galardini M, Jouhten P, Zelezniak A, Zeller G, Bork P, Typas A, Patil KR" +year: "2018" +journal: "Nat Microbiol" +volume: 3 +issue: 4 +pages: 514-522 +is_published: true +image: /assets/images/papers/nat-microbiol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1038/s41564-018-0123-9" +pmid: 29556107 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Bacterial metabolism plays a fundamental role in gut microbiota ecology and host-microbiome interactions. Yet the metabolic capabilities of most gut bacteria have remained unknown. Here we report growth characteristics of 96 phylogenetically diverse gut bacterial strains across 4 rich and 15 defined media. The vast majority of strains (76) grow in at least one defined medium, enabling accurate assessment of their biosynthetic capabilities. These do not necessarily match phylogenetic similarity, thus indicating a complex evolution of nutritional preferences. We identify mucin utilizers and species inhibited by amino acids and short-chain fatty acids. Our analysis also uncovers media for in vitro studies wherein growth capacity correlates well with in vivo abundance. Further value of the underlying resource is demonstrated by correcting pathway gaps in available genome-scale metabolic models of gut microorganisms. Together, the media resource and the extracted knowledge on growth abilities widen experimental and computational access to the gut microbiota. diff --git a/papers/_posts/2019-02-12-schmidt-extensive-transmission-of.md b/papers/_posts/2019-02-12-schmidt-extensive-transmission-of.md new file mode 100644 index 00000000..13d0e474 --- /dev/null +++ b/papers/_posts/2019-02-12-schmidt-extensive-transmission-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Extensive transmission of microbes along the gastrointestinal tract" +nickname: 2019-02-12-schmidt-extensive-transmission-of +authors: "Schmidt TS, Hayward MR, Coelho LP, Li SS, Costea PI, Voigt AY, Wirbel J, Maistrenko OM, Alves RJ, Bergsten E, de Beaufort C, Sobhani I, Heintz-Buschart A, Sunagawa S, Zeller G, Wilmes P, Bork P" +year: "2019" +journal: "Elife" +volume: 8 +issue: +pages: +is_published: true +image: /assets/images/papers/elife.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC6424576 +preprint: +supplement: + +# Links +doi: "10.7554/eLife.42693" +pmid: 30747106 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease. diff --git a/papers/_posts/2019-03-04-milanese-microbial-abundance-activity.md b/papers/_posts/2019-03-04-milanese-microbial-abundance-activity.md new file mode 100644 index 00000000..ce1c20cd --- /dev/null +++ b/papers/_posts/2019-03-04-milanese-microbial-abundance-activity.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Microbial abundance, activity and population genomic profiling with mOTUs2" +nickname: 2019-03-04-milanese-microbial-abundance-activity +authors: "Milanese A, Mende DR, Paoli L, Salazar G, Ruscheweyh HJ, Cuenca M, Hingamp P, Alves R, Costea PI, Coelho LP, Schmidt TSB, Almeida A, Mitchell AL, Finn RD, Huerta-Cepas J, Bork P, Zeller G, Sunagawa S" +year: "2019" +journal: "Nat Commun" +volume: 10 +issue: 1 +pages: 1014 +is_published: true +image: /assets/images/papers/nat-commun.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC6399450 +preprint: +supplement: + +# Links +doi: "10.1038/s41467-019-08844-4" +pmid: 30833550 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites). diff --git a/papers/_posts/2019-04-22-thomas-metagenomic-analysis-of.md b/papers/_posts/2019-04-22-thomas-metagenomic-analysis-of.md new file mode 100644 index 00000000..a926ae05 --- /dev/null +++ b/papers/_posts/2019-04-22-thomas-metagenomic-analysis-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation" +nickname: 2019-04-22-thomas-metagenomic-analysis-of +authors: "Thomas AM, Manghi P, Asnicar F, Pasolli E, Armanini F, Zolfo M, Beghini F, Manara S, Karcher N, Pozzi C, Gandini S, Serrano D, Tarallo S, Francavilla A, Gallo G, Trompetto M, Ferrero G, Mizutani S, Shiroma H, Shiba S, Shibata T, Yachida S, Yamada T, Wirbel J, Schrotz-King P, Ulrich CM, Brenner H, Arumugam M, Bork P, Zeller G, Cordero F, Dias-Neto E, Setubal JC, Tett A, Pardini B, Rescigno M, Waldron L, Naccarati A, Segata N" +year: "2019" +journal: "Nat Med" +volume: 25 +issue: 4 +pages: 667-678 +is_published: true +image: /assets/images/papers/nat-med.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC9533319 +preprint: +supplement: + +# Links +doi: "10.1038/s41591-019-0405-7" +pmid: 30936548 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Several studies have investigated links between the gut microbiome and colorectal cancer (CRC), but questions remain about the replicability of biomarkers across cohorts and populations. We performed a meta-analysis of five publicly available datasets and two new cohorts and validated the findings on two additional cohorts, considering in total 969 fecal metagenomes. Unlike microbiome shifts associated with gastrointestinal syndromes, the gut microbiome in CRC showed reproducibly higher richness than controls (P < 0.01), partially due to expansions of species typically derived from the oral cavity. Meta-analysis of the microbiome functional potential identified gluconeogenesis and the putrefaction and fermentation pathways as being associated with CRC, whereas the stachyose and starch degradation pathways were associated with controls. Predictive microbiome signatures for CRC trained on multiple datasets showed consistently high accuracy in datasets not considered for model training and independent validation cohorts (average area under the curve, 0.84). Pooled analysis of raw metagenomes showed that the choline trimethylamine-lyase gene was overabundant in CRC (P = 0.001), identifying a relationship between microbiome choline metabolism and CRC. The combined analysis of heterogeneous CRC cohorts thus identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies. diff --git a/papers/_posts/2019-04-22-wirbel-metaanalysis-of-fecal.md b/papers/_posts/2019-04-22-wirbel-metaanalysis-of-fecal.md new file mode 100644 index 00000000..ed838468 --- /dev/null +++ b/papers/_posts/2019-04-22-wirbel-metaanalysis-of-fecal.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer" +nickname: 2019-04-22-wirbel-metaanalysis-of-fecal +authors: "Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, Fleck JS, Voigt AY, Palleja A, Ponnudurai R, Sunagawa S, Coelho LP, Schrotz-King P, Vogtmann E, Habermann N, Nimeus E, Thomas AM, Manghi P, Gandini S, Serrano D, Mizutani S, Shiroma H, Shiba S, Shibata T, Yachida S, Yamada T, Waldron L, Naccarati A, Segata N, Sinha R, Ulrich CM, Brenner H, Arumugam M, Bork P, Zeller G" +year: "2019" +journal: "Nat Med" +volume: 25 +issue: 4 +pages: 679-689 +is_published: true +image: /assets/images/papers/nat-med.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC7984229 +preprint: +supplement: + +# Links +doi: "10.1038/s41591-019-0406-6" +pmid: 30936547 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 x 10(-5)). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics. diff --git a/papers/_posts/2019-07-01-sowah-effects-of-weightloss.md b/papers/_posts/2019-07-01-sowah-effects-of-weightloss.md new file mode 100644 index 00000000..918b5a0a --- /dev/null +++ b/papers/_posts/2019-07-01-sowah-effects-of-weightloss.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Effects of Weight-Loss Interventions on Short-Chain Fatty Acid Concentrations in Blood and Feces of Adults: A Systematic Review" +nickname: 2019-07-01-sowah-effects-of-weightloss +authors: "Sowah SA, Riedl L, Damms-Machado A, Johnson TS, Schubel R, Graf M, Kartal E, Zeller G, Schwingshackl L, Stangl GI, Kaaks R, Kuhn T" +year: "2019" +journal: "Adv Nutr" +volume: 10 +issue: 4 +pages: 673-684 +is_published: true +image: /assets/images/papers/adv-nutr.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC6628843 +preprint: +supplement: + +# Links +doi: "10.1093/advances/nmy125" +pmid: 31075175 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Short-chain fatty acids (SCFAs, mainly acetate, propionate, and butyrate), which are primarily derived from the gut microbiome, may exert anti-inflammatory and immunomodulatory effects, and regulate energy homeostasis. It has been suggested that weight loss may affect SCFA metabolism, but a systematic review of intervention studies is lacking. We aimed to systematically assess the effects of dietary, physical activity-based, and surgical weight-loss interventions among overweight [body mass index (BMI) 25-29.9 kg/m2)] or obese (BMI >/=30 kg/m2) adults (>/=18 y) on concentrations of acetate, propionate, butyrate, and total SCFAs in blood, urine, or feces. We conducted a systematic literature search in PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to April 30, 2018 for randomized and nonrandomized weight-loss trials among overweight or obese adults, in which the concentrations of individual and total SCFAs were assessed. A total of 9 studies consisting of 2 randomized parallel-arm trials, 4 crossover trials, and 3 nonrandomized clinical or surgical trials were included. In the majority of studies, changes in fecal SCFA concentrations were assessed, whereas changes in serum SCFAs were reported from 1 trial. Individual and total SCFA concentrations either remained unchanged or decreased significantly following weight loss. Three of the dietary interventions that resulted in decreased SCFA concentrations were low (33,000 species-level operational taxonomic units. To achieve this, we leveraged the reconstruction of >600,000 draft genomes, most of which are metagenome-assembled genomes (MAGs), from diverse microbiomes, including soil, freshwater systems, and the gastrointestinal tract of ruminants and other animals, which we found to be underrepresented by reference genomes. Overall, two thirds of all species-level taxa lacked a reference genome. The cumulative relative abundance of these newly included taxa was low in well-studied microbiomes, such as the human body sites (6-11%). By contrast, they accounted for substantial proportions (ocean, freshwater, soil: 43-63%) or even the majority (pig, fish, cattle: 60-80%) of the relative abundance across diverse non-human-associated microbiomes. Using community-developed benchmarks and datasets, we found mOTUs3 to be more accurate than other methods and to be more congruent with 16S rRNA gene-based methods for taxonomic profiling. Furthermore, we demonstrate that mOTUs3 increases the resolution of well-known microbial groups into species-level taxa and helps identify new differentially abundant taxa in comparative metagenomic studies. CONCLUSIONS: We developed mOTUs3 to enable accurate species-level profiling of metagenomes. Compared to other methods, it provides a more comprehensive view of prokaryotic community diversity, in particular for currently underexplored microbiomes. To facilitate comparative analyses by the research community, it is released with >11,000 precomputed profiles for publicly available metagenomes and is freely available at: https://github.com/motu-tool/mOTUs . Video Abstract. diff --git a/papers/_posts/2023-01-06-fullam-progenomes3-approaching-one.md b/papers/_posts/2023-01-06-fullam-progenomes3-approaching-one.md new file mode 100644 index 00000000..b07a8584 --- /dev/null +++ b/papers/_posts/2023-01-06-fullam-progenomes3-approaching-one.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "proGenomes3: approaching one million accurately and consistently annotated high-quality prokaryotic genomes" +nickname: 2023-01-06-fullam-progenomes3-approaching-one +authors: "Fullam A, Letunic I, Schmidt TSB, Ducarmon QR, Karcher N, Khedkar S, Kuhn M, Larralde M, Maistrenko OM, Malfertheiner L, Milanese A, Rodrigues JFM, Sanchis-Lopez C, Schudoma C, Szklarczyk D, Sunagawa S, Zeller G, Huerta-Cepas J, von Mering C, Bork P, Mende DR" +year: "2023" +journal: "Nucleic Acids Res" +volume: 51 +issue: D1 +pages: D760-D766 +is_published: true +image: /assets/images/papers/nucleic-acids-res.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC9825469 +preprint: +supplement: + +# Links +doi: "10.1093/nar/gkac1078" +pmid: 36408900 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +The interpretation of genomic, transcriptomic and other microbial 'omics data is highly dependent on the availability of well-annotated genomes. As the number of publicly available microbial genomes continues to increase exponentially, the need for quality control and consistent annotation is becoming critical. We present proGenomes3, a database of 907 388 high-quality genomes containing 4 billion genes that passed stringent criteria and have been consistently annotated using multiple functional and taxonomic databases including mobile genetic elements and biosynthetic gene clusters. proGenomes3 encompasses 41 171 species-level clusters, defined based on universal single copy marker genes, for which pan-genomes and contextual habitat annotations are provided. The database is available at http://progenomes.embl.de/. diff --git a/papers/_posts/2023-05-02-sambruni-location-and-condition.md b/papers/_posts/2023-05-02-sambruni-location-and-condition.md new file mode 100644 index 00000000..7877faa3 --- /dev/null +++ b/papers/_posts/2023-05-02-sambruni-location-and-condition.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Location and condition based reconstruction of colon cancer microbiome from human RNA sequencing data" +nickname: 2023-05-02-sambruni-location-and-condition +authors: "Sambruni G, Macandog AD, Wirbel J, Cagnina D, Catozzi C, Dallavilla T, Borgo F, Fazio N, Fumagalli-Romario U, Petz WL, Manzo T, Ravenda SP, Zeller G, Nezi L, Schaefer MH" +year: "2023" +journal: "Genome Med" +volume: 15 +issue: 1 +pages: 32 +is_published: true +image: /assets/images/papers/genome-med.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC10155404 +preprint: +supplement: + +# Links +doi: "10.1186/s13073-023-01180-9" +pmid: 37131219 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +BACKGROUND: The association between microbes and cancer has been reported repeatedly; however, it is not clear if molecular tumour properties are connected to specific microbial colonisation patterns. This is due mainly to the current technical and analytical strategy limitations to characterise tumour-associated bacteria. METHODS: Here, we propose an approach to detect bacterial signals in human RNA sequencing data and associate them with the clinical and molecular properties of the tumours. The method was tested on public datasets from The Cancer Genome Atlas, and its accuracy was assessed on a new cohort of colorectal cancer patients. RESULTS: Our analysis shows that intratumoural microbiome composition is correlated with survival, anatomic location, microsatellite instability, consensus molecular subtype and immune cell infiltration in colon tumours. In particular, we find Faecalibacterium prausnitzii, Coprococcus comes, Bacteroides spp., Fusobacterium spp. and Clostridium spp. to be strongly associated with tumour properties. CONCLUSIONS: We implemented an approach to concurrently analyse clinical and molecular properties of the tumour as well as the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk. diff --git a/papers/_posts/2023-05-04-larralde-pyhmmer-a-python.md b/papers/_posts/2023-05-04-larralde-pyhmmer-a-python.md new file mode 100644 index 00000000..4be9b87e --- /dev/null +++ b/papers/_posts/2023-05-04-larralde-pyhmmer-a-python.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "PyHMMER: a Python library binding to HMMER for efficient sequence analysis" +nickname: 2023-05-04-larralde-pyhmmer-a-python +authors: "Larralde M, Zeller G" +year: "2023" +journal: "Bioinformatics" +volume: 39 +issue: 5 +pages: +is_published: true +image: /assets/images/papers/bioinformatics.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC10159651 +preprint: +supplement: + +# Links +doi: "10.1093/bioinformatics/btad214" +pmid: 37074928 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +SUMMARY: PyHMMER provides Python integration of the popular profile Hidden Markov Model software HMMER via Cython bindings. This allows the annotation of protein sequences with profile HMMs and building new ones directly with Python. PyHMMER increases flexibility of use, allowing creating queries directly from Python code, launching searches, and obtaining results without I/O, or accessing previously unavailable statistics like uncorrected P-values. A new parallelization model greatly improves performance when running multithreaded searches, while producing the exact same results as HMMER. AVAILABILITY AND IMPLEMENTATION: PyHMMER supports all modern Python versions (Python 3.6+) and similar platforms as HMMER (x86 or PowerPC UNIX systems). Pre-compiled packages are released via PyPI (https://pypi.org/project/pyhmmer/) and Bioconda (https://anaconda.org/bioconda/pyhmmer). The PyHMMER source code is available under the terms of the open-source MIT licence and hosted on GitHub (https://github.com/althonos/pyhmmer); its documentation is available on ReadTheDocs (https://pyhmmer.readthedocs.io). diff --git a/papers/_posts/2023-08-22-ducarmon-remodelling-of-the.md b/papers/_posts/2023-08-22-ducarmon-remodelling-of-the.md new file mode 100644 index 00000000..fbb18bfa --- /dev/null +++ b/papers/_posts/2023-08-22-ducarmon-remodelling-of-the.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Remodelling of the intestinal ecosystem during caloric restriction and fasting" +nickname: 2023-08-22-ducarmon-remodelling-of-the +authors: "Ducarmon QR, Grundler F, Le Maho Y, Wilhelmi de Toledo F, Zeller G, Habold C, Mesnage R" +year: "2023" +journal: "Trends Microbiol" +volume: 31 +issue: 8 +pages: 832-844 +is_published: true +image: /assets/images/papers/trends-microbiol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: +preprint: +supplement: + +# Links +doi: "10.1016/j.tim.2023.02.009" +pmid: 37031065 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Benefits of fasting and caloric restriction on host metabolic health are well established, but less is known about the effects on the gut microbiome and how this impacts renewal of the intestinal mucosa. What has been repeatedly shown during fasting, however, is that bacteria utilising host-derived substrates proliferate at the expense of those relying on dietary substrates. Considering the increased recognition of the gut microbiome's role in maintaining host (metabolic) health, disentangling host-microbe interactions and establishing their physiological relevance in the context of fasting and caloric restriction is crucial. Such insights could aid in moving away from associations of gut bacterial signatures with metabolic diseases consistently reported in observational studies to potentially establishing causality. Therefore, this review aims to summarise what is currently known or still controversial about the interplay between fasting and caloric restriction, the gut microbiome and intestinal tissue physiology. diff --git a/papers/_posts/2023-11-22-cacace-systematic-analysis-of.md b/papers/_posts/2023-11-22-cacace-systematic-analysis-of.md new file mode 100644 index 00000000..b7c12fa5 --- /dev/null +++ b/papers/_posts/2023-11-22-cacace-systematic-analysis-of.md @@ -0,0 +1,40 @@ +--- +layout: paper +title: "Systematic analysis of drug combinations against Gram-positive bacteria" +nickname: 2023-11-22-cacace-systematic-analysis-of +authors: "Cacace E, Kim V, Varik V, Knopp M, Tietgen M, Brauer-Nikonow A, Inecik K, Mateus A, Milanese A, Marli MT, Mitosch K, Selkrig J, Brochado AR, Kuipers OP, Kjos M, Zeller G, Savitski MM, Gottig S, Huber W, Typas A" +year: "2023" +journal: "Nat Microbiol" +volume: 8 +issue: 11 +pages: 2196-2212 +is_published: true +image: /assets/images/papers/nat-microbiol.png +projects: +tags: [] + +# Text +fulltext: +pdf: +pdflink: +pmcid: PMC10627819 +preprint: +supplement: + +# Links +doi: "10.1038/s41564-023-01486-9" +pmid: 37770760 + +# Data and code +github: +neurovault: +openneuro: +figshare: +figshare_names: +osf: +--- +{% include JB/setup %} + +# Abstract + +Drug combinations can expand options for antibacterial therapies but have not been systematically tested in Gram-positive species. We profiled ~8,000 combinations of 65 antibacterial drugs against the model species Bacillus subtilis and two prominent pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Thereby, we recapitulated previously known drug interactions, but also identified ten times more novel interactions in the pathogen S. aureus, including 150 synergies. We showed that two synergies were equally effective against multidrug-resistant S. aureus clinical isolates in vitro and in vivo. Interactions were largely species-specific and synergies were distinct from those of Gram-negative species, owing to cell surface and drug uptake differences. We also tested 2,728 combinations of 44 commonly prescribed non-antibiotic drugs with 62 drugs with antibacterial activity against S. aureus and identified numerous antagonisms that might compromise the efficacy of antimicrobial therapies. We identified even more synergies and showed that the anti-aggregant ticagrelor synergized with cationic antibiotics by modifying the surface charge of S. aureus. All data can be browsed in an interactive interface ( https://apps.embl.de/combact/ ).