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.
Note: this may seem like a slight barrier to entry, but it's as simple as running a single shell command. That being said, we plan to begin releasing pre-compiled binaries for several platforms in the next release
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 uses subcommands.
Currently, there is only one subcommand: search
*Note: that may seem a little strange, but we will be adding subcommands in the near future
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 ./tmp/ directory.
For example, when running nail search, you'll see something like:
$ nail search query.hmm target.fa
reading query database... done (0.00s)
indexing target database... done (0.00s)
running mmseqs... done (0.44s)
running nail pipeline... done (0.16s)
Checking the results.tbl will 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
nail can also produce alignment output if you supply an --ali-out argument:
$ nail search --ali-out results.ali query.hmm target.fa
Checking the results.ali will look something like:
$ head -n 70 results.ali
query: 7tm_1
target: O08892|reviewed|5-hydroxytryptamine
query start: 2
query end: 260
target start: 66
target end: 368
score: 257.7
comp bias: 9.3
E-value: 6.3e-79
cell frac: 0.094
==
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 144
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 145 DRYWAITDAVGYSAKRTPRRAAGMIALVWVFSICISLPPFFWRQAKAE---EEVLDCLVNTDH------VLYTVYSTGGA 215
*****************************************777666500099******99990000009**********
7tm_1 162 fllpllvilvcyvrilrtlrksakkeks.................................................... 189
f+lp+l+++ +y ri+ ++r++ k++
O08892|reviewed|5-hydroxytryptamine 216 FYLPTLLLIALYGRIYVEARSRILKQTPNKTGKRLTRAQLITDSPGSTSSVTSINSRAPEVPCDSGSPVYVNQVKVRVSD 295
***********************9999899999999999999999999********************************
7tm_1 190 ....rkkksarkerkalktllvvvvvfvlcwlPyfilllldsllkeceseklve.tallitlllayvnsclNPiiY 260
+kk +a++erka+ktl+v++++f++cwlP+fi++l++ + c++ + + ++++++++l+y+ns++NPiiY
O08892|reviewed|5-hydroxytryptamine 296 ALLEKKKLMAARERKATKTLGVILGAFIVCWLPFFIISLVMPI---CKDACWFHMAIFDFFTWLGYLNSLINPIIY 368
***9999************************************000777666551666******************
//
query: 7tm_1
target: O02666|reviewed|Alpha-1D
query start: 1
query end: 260
target start: 118
target end: 407
score: 255.6
comp bias: 5.5
E-value: 2.8e-78
cell frac: 0.061
==
7tm_1 1 gNllVilvilrnkklrtptnifllnLavaDllvlllvlpfslvyallegdwvfgevlCklvtaldvvnltasillltais 80
gNllVil +++n++l+t+tn+f++nLavaDll++++vlpfs++ ++l g w fg+++C+++ a+dv+++tasil+l+ is
O02666|reviewed|Alpha-1D 118 GNLLVILSVACNRHLQTVTNYFIVNLAVADLLLSATVLPFSATMEVL-GFWAFGRAFCDVWAAVDVLCCTASILSLCTIS 196
8*********************************************70********************************
7tm_1 81 iDRYlaIvkplkykrirtkrralvlilvvWvlalllslppllfsgtktesaekeetvClidfpeeestwevsytlllsvl 160
+DRY+ + + lky++i+t r+a++++++ W++al++s+ pll g+k+ + +e++C i+ + y++++s++
O02666|reviewed|Alpha-1D 197 VDRYVGVRHSLKYPAIMTERKAAAILALLWAVALVVSMGPLL--GWKEPVP-PDERFCGITEEV-------GYAVFSSLC 266
******************************************00677776609*******87650000000*********
7tm_1 161 gfllpllvilvcyvrilrtlrksakkeks............................................rkkksar 196
+f+lp+ vi+v+y+r++ +r++ ++ + + +++
O02666|reviewed|Alpha-1D 267 SFYLPMAVIVVMYCRVYVVARSTTRSLEAGVKRERGKASEVVLRIHCRGAASGADGAPGTRGAKGHTFRSSLSVRLLKFS 346
***************************99999999999999999999999999999999999999999999986677778
7tm_1 197 kerkalktllvvvvvfvlcwlPyfilllldsllkeceseklvetallitlllayvnsclNPiiY 260
+e+ka+ktl++vv+vfvlcw+P+f++l l sl ++ k +e +++++ +l+y+nsc+NP+iY
O02666|reviewed|Alpha-1D 347 REKKAAKTLAIVVGVFVLCWFPFFFVLPLGSL---FPQLKPSEGVFKVIFWLGYFNSCVNPLIY 407
899*****************************0009****************************
//
...
...
...
If you run nail search --only-seed command, nail will run MMseqs2, produces seeds.json file, and terminate.
This may be useful if you would like to experiment with different nail settings using the same seeds.
For example:
$ nail search --only-seed query.hmm target.fa
You can also save the seeds from a full run of the nail search pipeline by supplying a --seeds-out argument:
$ nail search --seeds-out seeds.json 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, // <- these are the positions from which
"target_end": 287, // < nail will begin the cloud search
"profile_start": 1, // <
"profile_end": 259, // <
"score": 168.0 // <--- the score field is used to pick between
}, seeds that compete with each other
"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
},
}
...
}
We plan to make the use of custom seeds more robust in the future.
nail is licensed under the BSD-3-Clause license.
See LICENSE for details.
Jack Roddy - [email protected]