Merge branch 'dev'
This commit is contained in:
Heng Li
commit
dbe74ca9b8
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@ -156,14 +156,16 @@ have ignored these important genes.
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We recommend to include the genomic regions of classical HLA genes in the BWA
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index. This way we will be able to get a more complete collection of reads
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mapped to HLA. We can then isolate these reads with little computational cost
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and type HLA genes with another program, such as [Dilthey et al (2014)][hla1] or
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one from [this list][hlatools].
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and type HLA genes with another program, such as [Warren et al (2012)][hla4],
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[Liu et al (2013)][hla2], [Bai et al (2014)][hla3], [Dilthey et al (2014)][hla1]
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or others from [this list][hlatools].
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If the postprocessing script `bwa-postalt.js` is invoked with `-p prefix`, it
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will also write the top three alleles to file `prefix.hla`. However, as most HLA
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alleles from IMGT/HLA don't have intronic sequences and thus are not included in
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the reference genome, we are unable to type HLA genes to high resolution with
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the BWA-MEM mapping alone. A dedicated tool is recommended for accurate typing.
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the BWA index from option 2, we are unable to type HLA genes to high resolution
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with the BWA-MEM mapping alone. A dedicated tool is recommended for accurate
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typing.
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### Evaluating ALT Mapping
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@ -194,3 +196,6 @@ can even get rid of ALT contigs for good.
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[hla1]: http://biorxiv.org/content/early/2014/07/08/006973
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[hlalink]: http://www.hladiseaseassociations.com
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[hlatools]: https://www.biostars.org/p/93245/
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[hla2]: http://nar.oxfordjournals.org/content/41/14/e142.full.pdf+html
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[hla3]: http://www.biomedcentral.com/1471-2164/15/325
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[hla4]: http://genomemedicine.com/content/4/12/95
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113
bwa-postalt.js
113
bwa-postalt.js
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@ -203,42 +203,18 @@ function parse_hit(s, opt)
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return h;
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}
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function type_hla(w)
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function print_buffer(buf2, fp_hla, hla)
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{
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var hla = ["A", "B", "C", "DQA1", "DQB1", "DRB1"];
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var hla_hash = {}, a = [], r = [];
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for (var i = 0; i < hla.length; ++i) {
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hla_hash[hla[i]] = i;
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a[i] = [];
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}
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for (var i = 0; i < w.length; ++i) {
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var t = w[i][0].split(/[:\*]/);
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var x = hla_hash[t[0]];
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if (x != null)
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a[x].push([w[i][0], t[1], t[1] + ':' + t[2], w[i][1]]);
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}
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for (var k = 1; k <= 2; ++k) {
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for (var i = 0; i < hla.length; ++i) {
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var ai = a[i], m = {};
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for (var j = 0; j < ai.length; ++j) {
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var key = ai[j][k], val = ai[j][3];
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if (m[key] == null) m[key] = [-1, -1.0];
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if (m[key][1] < val) m[key] = [j, val];
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}
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var sum = 0;
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for (var x in m) sum += m[x][1];
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var max = -1, max2 = -1, max3 = -1, max_x, max_x2, max_x3;
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for (var x in m) {
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if (max < m[x][1]) max3 = max2, max_x3 = max_x2, max2 = max, max_x2 = max_x, max = m[x][1], max_x = x;
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else if (max2 < m[x][1]) max3 = max2, max_x3 = max_x2, max2 = m[x][1], max_x2 = x;
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else if (max3 < m[x][1]) max3 = m[x][1], max_x3 = x;
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}
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r.push([hla[i], k, hla[i]+'*'+max_x, max.toFixed(3), hla[i]+'*'+max_x2, max2.toFixed(3), hla[i]+'*'+max_x3, max3.toFixed(3)]);
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if (buf2.length == 0) return;
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for (var i = 0; i < buf2.length; ++i)
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print(buf2[i].join("\t"));
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if (fp_hla != null) {
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var name = buf2[0][0] + '/' + (buf2[0][1]>>6&3) + ((buf2[0][1]&16)? '-' : '+');
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for (var x in hla) {
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if (fp_hla[x] != null);
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fp_hla[x].write('@' + name + '\n' + buf2[0][9] + '\n+\n' + buf2[0][10] + '\n');
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}
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}
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for (var i = 0; i < r.length; ++i)
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print(r[i].join("\t"));
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return r;
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}
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function bwa_postalt(args)
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@ -285,7 +261,7 @@ function bwa_postalt(args)
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var buf = new Bytes();
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// read ALT-to-REF alignment
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var intv_alt = {}, intv_pri = {}, idx_un = {};
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var intv_alt = {}, intv_pri = {}, idx_un = {}, hla_ctg = {};
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var file = new File(args[getopt.ind]);
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while (file.readline(buf) >= 0) {
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var line = buf.toString();
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@ -299,6 +275,10 @@ function bwa_postalt(args)
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continue;
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}
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var m, cigar = [], l_qaln = 0, l_tlen = 0, l_qclip = 0;
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if ((m = /^(HLA-[^\s\*]+)\*\d+/.exec(t[0])) != null) { // read HLA contigs
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if (hla_ctg[m[1]] == null) hla_ctg[m[1]] = 0;
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++hla_ctg[m[1]];
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}
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while ((m = re_cigar.exec(t[5])) != null) {
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var l = parseInt(m[1]);
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cigar.push([m[2] != 'H'? m[2] : 'S', l]); // convert hard clip to soft clip
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@ -321,6 +301,14 @@ function bwa_postalt(args)
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for (var ctg in intv_pri)
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idx_pri[ctg] = intv_ovlp(intv_pri[ctg]);
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// initialize the list of HLA contigs
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var fp_hla = null;
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if (opt.pre) {
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fp_hla = {};
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for (var h in hla_ctg)
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fp_hla[h] = new File(opt.pre + '.' + h + '.fq', "w");
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}
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// initialize the list of ALT contigs
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var weight_alt = [];
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for (var ctg in idx_alt)
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@ -329,7 +317,7 @@ function bwa_postalt(args)
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weight_alt[ctg] = [0, 0, 0, 0, 0, 0, '~', 0, 0];
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// process SAM
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var buf2 = [];
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var buf2 = [], hla = {};
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file = args.length - getopt.ind >= 2? new File(args[getopt.ind+1]) : new File();
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while (file.readline(buf) >= 0) {
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var m, line = buf.toString();
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@ -343,9 +331,8 @@ function bwa_postalt(args)
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// print bufferred reads
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if (buf2.length && (buf2[0][0] != t[0] || (buf2[0][1]&0xc0) != (t[1]&0xc0))) {
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for (var i = 0; i < buf2.length; ++i)
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print(buf2[i].join("\t"));
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buf2 = [];
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print_buffer(buf2, fp_hla, hla);
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buf2 = [], hla = {};
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}
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// skip unmapped lines
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@ -468,27 +455,35 @@ function bwa_postalt(args)
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else mapQ = mapQ > ori_mapQ? mapQ : ori_mapQ;
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} else mapQ = t[4];
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var pri_ofunc = idx_pri[hits[reported_i].pctg], ovlp_alt = [];
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if (pri_ofunc != null) {
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var rpt_start = 1<<30, rpt_end = 0;
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for (var i = 0; i < hits.length; ++i) {
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var h = hits[i];
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if (h.g == reported_g) {
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rpt_start = rpt_start < h.pstart? rpt_start : h.pstart;
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rpt_end = rpt_end > h.pend ? rpt_end : h.pend;
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}
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}
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ovlp_alt = pri_ofunc(rpt_start, rpt_end);
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for (var i = 0; i < ovlp_alt.length; ++i)
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if ((m = /^(HLA-[^\s\*]+)\*\d+/.exec(ovlp_alt[i][2])) != null)
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hla[m[1]] = true;
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}
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// ALT genotyping
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if (mapQ >= opt.min_mapq && hits[reported_i].score >= opt.min_sc) {
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// collect all overlapping ALT contigs
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var hits2 = [];
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var alts = {};
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for (var i = 0; i < hits.length; ++i) {
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var h = hits[i];
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if (h.g == reported_g)
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hits2.push([h.pctg, h.pstart, h.pend, h.ctg, h.score, h.NM]);
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if (h.g == reported_g && weight_alt[h.ctg] != null)
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alts[h.ctg] = [h.score, h.NM];
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}
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var start = hits2[0][1], end = hits2[0][2];
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for (var i = 1; i < hits2.length; ++i)
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end = end > hits2[i][2]? end : hits2[i][2];
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var alts = {};
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for (var i = 0; i < hits2.length; ++i)
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if (weight_alt[hits2[i][3]] != null)
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alts[hits2[i][3]] = [hits2[i][4], hits2[i][5]];
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if (idx_pri[hits2[0][0]] != null) { // add other unreported hits
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var ovlp = idx_pri[hits2[0][0]](start, end);
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for (var i = 0; i < ovlp.length; ++i)
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if (ovlp[i][0] <= start && end <= ovlp[i][1] && alts[ovlp[i][2]] == null)
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alts[ovlp[i][2]] = [0, 0];
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if (ovlp_alt.length > 0) { // add other unreported hits
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for (var i = 0; i < ovlp_alt.length; ++i)
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if (ovlp_alt[i][0] <= rpt_start && rpt_end <= ovlp_alt[i][1] && alts[ovlp_alt[i][2]] == null)
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alts[ovlp_alt[i][2]] = [0, 0];
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}
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// add weight to each ALT contig
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@ -600,10 +595,12 @@ function bwa_postalt(args)
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buf2.push(s);
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}
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}
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for (var i = 0; i < buf2.length; ++i)
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print(buf2[i].join("\t"));
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print_buffer(buf2, fp_hla, hla);
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file.close();
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if (fp_evi != null) fp_evi.close();
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if (fp_hla != null)
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for (var h in fp_hla)
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fp_hla[h].close();
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buf.destroy();
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aux.destroy();
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@ -628,12 +625,6 @@ function bwa_postalt(args)
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fpout.write(weight_arr[i].join("\t") + '\n');
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}
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fpout.close();
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var r = type_hla(weight_hla);
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fpout = new File(opt.pre + '.hla', "w");
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for (var i = 0; i < r.length; ++i)
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fpout.write(r[i].join("\t") + '\n');
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fpout.close();
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}
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}
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