bioseq-js

A Fast, Lightweight Smith-Waterman Sequence Aligner

Use

Demo

Click here to try it out.

Installation

bioseq is packaged as a module for Node environments, but automatically attaches itself to window if included in a browser. To get it in Node, from your project directory,

npm install bioseq --save

From there, you can require it wherever is convenient:

const bioseq = require("bioseq");

Alternately, if you just want it in the browser, download it and include it with a script tag, like so:

<script src="bioseq.js"></script>

Quick Start Example

var target = "ATAGCTAGCTAGCATAAGC";
var query = "AGCTAcCGCAT";

var rst = bioseq.align(target, query);

console.log("Score: ", rst.score);
console.log("Starting position: ", rst.position);
console.log("CIGAR: ", bioseq.cigar2str(rst.CIGAR));

var fmt = bioseq.cigar2gaps(target, query, rst.position, rst.CIGAR);

console.log(fmt[0]);
console.log(fmt[1]);

For a more comprehensive example, view the source of demo/index.html

API

bioseq is an object with the following functions: align, cigar2gaps, cigar2str, bsg_enc_seq, gen_query_profile, gen_score_matrix, makeAlphabetMap, and makeIntArray.

In general, the only functions of general interest are align and cigar2*, so let's talk about those.

bioseq.align

align is the fundamental function of bioseq. It accepts seven parameters:

• reference - the reference sequence
• query - the query sequence or profile

And, optionally:

• is_local - perform local alignment
• matrix - square score matrix or [match,mismatch] array
• gapsc - [gap_open,gap_ext] array; k-length gap costs gap_open+gap_ext
• w - bandwidth, disabled by default
• table - encoding table. It defaults to bioseq.nt5.

Returns an object containing a score, position, and CIGAR. CIGAR is encoded in the BAM way, where higher 28 bits keeps the length and lower 4 bits the operation in order of 'MIDNSH'. See bioseq.cigar2str() for converting CIGAR to string.

bioseq.cigar2str

Before I get in to what this function does, let's talk about what it needs. CIGAR is an encoding scheme for sequence alignment instructions. Basically, it's a list of instructions to make two sequences line up. These instructions are assembled from a very simple set:

• M for match
• I for insertion
• D for deletion
• N for gap
• S for substitution
• H for hard clipping

Each of these can be preceded by an integer, indicating the number of base pairs for which this instruction is correct between the two sequences. However, CIGARs are stored as simpler machine instructions, rather than strings. So, if you want to show the CIGAR (for some reason), you're going to need this.

bioseq.cigar2gaps

Takes a pair of sequences and a CIGAR and returns an array of sequences which have been aligned according to the instructions in the CIGAR.

• reference - The same reference sequence you passed to bioseq.align
• query - The same query you passed to bioseq.align
• start - The position value of the object returned by bioseq.align
• cigar - The CIGAR value of the object retruned by bioseq.align

And optionally,

• fixed - A boolean indicating whether the reference is fixed or modifiable. Basically, if you're aligning many sequences to the same reference, you should set fixed to true. Otherwise you can just leave it out.

Theory

bioseq implements local and global pairwise alignment with affine gap penalties. There are two formulations: the Durbin formulation as is described in his book and the Green formulation as is implemented in phrap. The Durbin formulation is easier to understand, while the Green formulation is simpler to code and probably faster in practice.

The Durbin formulation is:

M(i,j) = max{M(i-1,j-1)+S(i,j), E(i-1,j-1), F(i-1,j-1)}

E(i,j) = max{M(i-1,j)-q-r, F(i-1,j)-q-r, E(i-1,j)-r}

F(i,j) = max{M(i,j-1)-q-r, F(i,j-1)-r, E(i,j-1)-q-r}

where q is the gap open penalty, r the gap extension penalty and S(i,j) is the score between the i-th residue in the row sequence and the j-th residue in the column sequence. Note that the original Durbin formulation disallows transitions between between E and F states, but we allow them here.

In the Green formulation, we introduce:

H(i,j) = max{M(i,j), E(i,j), F(i,j)}

The recursion becomes:

H(i,j) = max{H(i-1,j-1)+S(i,j), E(i,j), F(i,j)}

E(i,j) = max{H(i-1,j)-q, E(i-1,j)} - r

F(i,j) = max{H(i,j-1)-q, F(i,j-1)} - r

It is in fact equivalent to the Durbin formulation. In implementation, we calculate the scores in a different order:

H(i,j)   = max{H(i-1,j-1)+S(i,j), E(i,j), F(i,j)}

E(i+1,j) = max{H(i,j)-q, E(i,j)} - r

F(i,j+1) = max{H(i,j)-q, F(i,j)} - r

i.e. at cell (i,j), we compute E for the next row and F for the next column.

History

In an online conversation, Istvan Albert was complaining he could not find a good Smith-Waterman implementation in Javascript. Li Heng thought he could write one over night by porting ksw.c to javascript. It took longer than he planned because he found a couple of subtle bugs in ksw.c. And while he was porting the C code to javascript, he realized that it is not that difficult to merge local and banded global alignments in one function. Achieving that also took extra time.

The end product is a fast and lightweight javascript library for affine-gap local and banded global pairwise alignment. With a modern Javascript engine, it is not much slower than a non-SSE C implementation.

This repository adapted Li's original algorithm for release on NPM. Li did all the hard work, and we owe him a large debt of gratitude for it.

Public Domain

This repository constitutes a work of the United States Government and is not subject to domestic copyright protection under 17 USC § 105. This repository is in the public domain within the United States, and copyright and related rights in the work worldwide are waived through the CC0 1.0 Universal public domain dedication. All contributions to this repository will be released under the CC0 dedication. By submitting a pull request you are agreeing to comply with this waiver of copyright interest.

License

The repository utilizes code licensed under the terms of the Apache Software License and therefore is licensed under ASL v2 or later.

This source code in this repository is free: you can redistribute it and/or modify it under the terms of the Apache Software License version 2, or (at your option) any later version.

This source code in this repository is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the Apache Software License for more details.

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The source code forked from other open source projects will inherit its license.

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Notices

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