This is a cargo workspace for nail, which is a profile Hidden Markov Model (pHMM) biological sequence alignment tool. Using the fast MMseqs2 search pipeline to produce candidate alignment seeds, nail computes a fast approximation of the HMMER3 Forward/Backward (F/B) sequence alignment algorithm. Currently, nail only supports amino acid search, with nucleotide search coming in a future update.
The nail preprint paper can be found on bioRxiv (doi: https://doi.org/10.1101/2024.01.27.577580).
There are two sub-projects in the nail workspace:
nail: this is the command line toollibnail: this is a Rust library that contains the implementation of nail's sparse alignment algorithms
A few example input files may be found under the fixtures/ directory at the root of this repository.
$ ls fixtures/
query.fa target.fa query.hmm
The nail search pipeline uses the mmseqs search tool as an alignment prefilter.
In the future, we will replace this with our own prefiltering strategies.
nail has been tested with MMseqs2 Release 15-6f452. We have not tested nail against other versions of MMseqs2, but they may work.
To run the nail search pipeline, mmseqs search must be available in your system path.
To install nail, you'll need the Rust development tooling, which means you'll need to install the Rust compiler and Cargo. The easiest way to do that is to use rustup.
Once Cargo is installed, you can install nail with:
cargo install nail
If you'd like to build nail from source, you can clone this repository and build the project with Cargo:
git clone https://github.com/TravisWheelerLab/nail
cd nail/
cargo build --release
You'll then find the compiled binary at: target/release/nail
For example, try running:
target/release/nail -h
The nail command line interface has two subcommands: search and seed.
The nail search command runs the entire nail pipeline, including running MMseqs2 to find alignment seeds.
The input to nail search is a query file (p7HMM or FASTA) and a target sequence database file (FASTA).
By default, the search results will be written to ./results.tbl in a tabular format, and alignment output is written to stdout.
In addition, a collection of temporary files required to run mmseqs search, will be written to the ./prep/ directory.
For example, when running nail search, you'll see something like:
$ nail search query.hmm target.fa
== score: 257.1 bits; E-value: 9.7e-79
7tm_1 2 NllVilvilrnkklrtptnifllnLavaDllvlllvlpfslvyallegdwvfgevlCklvtaldvvnltasillltaisi 81
N +Vi++++r++kl+tp+n+++ +La++Dllv++lv+p+s++y++ +g+w++g++lC+++ + d++++tasi++l++i++
O08892|reviewed|5-hydroxytryptamine 66 NAFVIATVYRTRKLHTPANYLIASLAFTDLLVSILVMPISTMYTV-TGRWTLGQALCDFWLSSDITCCTASIMHLCVIAL 145
9********************************************06*********************************
7tm_1 82 DRYlaIvkplkykrirtkrralvlilvvWvlalllslppllfsgtktesaekeetvClidfpeeestwevsytlllsvlg 161
DRY+aI+ ++ y+++rt+rra+ +i++vWv+++++slpp+++++ k e +e+ Cl+++++ v yt++++ ++
O08892|reviewed|5-hydroxytryptamine 146 DRYWAITDAVGYSAKRTPRRAAGMIALVWVFSICISLPPFFWRQAKAE---EEVLDCLVNTDH------VLYTVYSTGGA 225
*****************************************777666500099******99990000009**********
7tm_1 162 fllpllvilvcyvrilrtlrksakkeks.................................................... 241
f+lp+l+++ +y ri+ ++r++ k++
O08892|reviewed|5-hydroxytryptamine 226 FYLPTLLLIALYGRIYVEARSRILKQTPNKTGKRLTRAQLITDSPGSTSSVTSINSRAPEVPCDSGSPVYVNQVKVRVSD 305
***********************9999899999999999999999999********************************
7tm_1 242 ....rkkksarkerkalktllvvvvvfvlcwlPyfilllldsllkeceseklve.tallitlllayvnsclNPiiY 317
+kk +a++erka+ktl+v++++f++cwlP+fi++l++ + c++ + + ++++++++l+y+ns++NPiiY
O08892|reviewed|5-hydroxytryptamine 306 ALLEKKKLMAARERKATKTLGVILGAFIVCWLPFFIISLVMPI---CKDACWFHMAIFDFFTWLGYLNSLINPIIY 381
***9999************************************000777666551666******************
...
...
...
Checking the results.tbl might look something like:
$ head -n 15 results.bl
# target target query query comp cell
# target query start end start end score bias evalue frac
# ------------------------------------------------------- --------------- ------ ------ ----- ----- ----- ---- ------- -----
F1MV99|reviewed|Somatostatin 7tm_1-consensus 58 306 1 260 175.8 7.5 1.0e-53 0.066
O08858|reviewed|Somatostatin 7tm_1-consensus 54 303 1 260 173.0 7.8 7.7e-53 0.069
C3ZQF9|reviewed|QRFP-like 7tm_1-consensus 64 326 1 260 149.3 8.6 1.3e-45 0.070
O02813|reviewed|Neuropeptide 7tm_1-consensus 56 319 1 260 147.9 5.4 3.5e-45 0.070
O08565|reviewed|C-X-C 7tm_1-consensus 52 299 1 260 145.8 5.3 1.5e-44 0.076
O02835|reviewed|Neuropeptide 7tm_1-consensus 57 320 1 260 145.7 6.8 1.6e-44 0.071
A0T2N3|reviewed|Apelin 7tm_1-consensus 51 316 1 260 145.0 4.3 2.6e-44 0.077
O08726|reviewed|Galanin 7tm_1-consensus 42 292 1 260 144.9 4.2 2.8e-44 0.073
O08556|reviewed|C-C 7tm_1-consensus 49 299 1 260 144.3 5.3 4.4e-44 0.073
F1R332|reviewed|Galanin 7tm_1-consensus 35 286 1 260 143.3 3.8 8.9e-44 0.077
D4A7K7|reviewed|G-protein 7tm_1-consensus 44 304 1 260 142.7 4.3 1.3e-43 0.073
E7F7V7|reviewed|Galanin 7tm_1-consensus 43 294 1 260 142.6 1.7 1.4e-43 0.073
The nail seed command runs MMseqs2 and produces a seeds.json file.
For example:
$ nail seed query.hmm target.fa
Seeds can be provided to nail search using the --seeds <seeds.json> flag, which will skip the seed step in the search pipeline.
$ nail search --seeds seeds.json query.hmm target.fa
In practice, these seeds may be produced from any source as long as they are formatted in the following way:
{
"query1": {
"target1": {
"target_start": 48,
"target_end": 287,
"profile_start": 1,
"profile_end": 259,
"score": 168.0
},
"target2": {
"target_start": 72,
"target_end": 343,
"profile_start": 23,
"profile_end": 259,
"score": 106.0
},
"query2": {
"target3": {
"target_start": 56,
"target_end": 303,
"profile_start": 1,
"profile_end": 259,
"score": 125.0
},
}
...
}
nail is licensed under the BSD-3-Clause license.
See LICENSE for details.
Jack Roddy - jroddy@arizona.edu
