var fuzzy = 3, min_qal = 100, drop_thres = 7; var file = arguments.length == 0? new File () : new File(arguments[0]); var buf = new Bytes(); var re_cigar = /(\d+)([MIDSH])/g; var len = {}, list = [], gcnt = []; while (file.readline(buf) >= 0) { var m, mm, line = buf.toString(); var t = line.split("\t"); if (t[0].charAt(0) == '@') { if (t[0] == '@SQ' && (m = /LN:(\d+)/.exec(line)) != null && (mm = /SN:(\S+)/.exec(line)) != null) len[mm[1]] = parseInt(m[1]); continue; } var gene = null, exon = null; if ((m = /^(HLA-[^\s_]+)_(\d+)/.exec(t[0])) != null) { gene = m[1], exon = parseInt(m[2]) - 1; if (gcnt[exon] == null) gcnt[exon] = {}; gcnt[exon][gene] = true; } if (gene == null || exon == null || t[2] == '*') continue; var x = 0, ts = parseInt(t[3]) - 1, te = ts, clip = [0, 0]; while ((m = re_cigar.exec(t[5])) != null) { var l = parseInt(m[1]); if (m[2] == 'M') x += l, te += l; else if (m[2] == 'I') x += l; else if (m[2] == 'D') te += l; else if (m[2] == 'S' || m[2] == 'H') clip[x==0?0:1] = l; } if (x < min_qal && clip[0] + clip[1] > 0) continue; var tl = len[t[2]]; var left = ts < clip[0]? ts : clip[0]; var right = tl - te < clip[1]? tl - te : clip[1]; var nm = (m = /\tNM:i:(\d+)/.exec(line)) != null? parseInt(m[1]) : 0; list.push([t[2], gene, exon, ts, te, nm, left + right]); } buf.destroy(); file.close(); // identify the primary exon(s) var pri_exon = [], n_pri_exons; { var cnt = [], max = 0; for (var e = 0; e < gcnt.length; ++e) { if (gcnt[e] != null) { var c = 0, h = gcnt[e]; for (var x in h) ++c; cnt[e] = c; max = max > c? max : c; } else cnt[e] = 0; } var pri_list = []; for (var e = 0; e < cnt.length; ++e) { if (cnt[e] == max) pri_list.push(e + 1); pri_exon[e] = cnt[e] == max? 1 : 0; } warn("List of primary exons: ["+pri_list.join(",")+"]"); n_pri_exons = pri_list.length; } // convert strings to integers (for performance) var ghash = {}, glist = [], chash = {}, clist = [], elist = []; for (var i = 0; i < list.length; ++i) { var g = glist.length, c = clist.length; if (ghash[list[i][1]] == null) { glist.push(list[i][1]); ghash[list[i][1]] = g; } if (chash[list[i][0]] == null) { clist.push(list[i][0]); chash[list[i][0]] = c; } if (elist[g] == null) elist[g] = {}; elist[g][list[i][2]] = true; } // change to the per-exon representation var exons = []; for (var i = 0; i < list.length; ++i) { var li = list[i]; if (exons[li[2]] == null) exons[li[2]] = []; exons[li[2]].push([chash[li[0]], ghash[li[1]], li[5] + li[6]]); } // initialize genotype scores var pair = []; for (var i = 0; i < glist.length; ++i) { pair[i] = []; for (var j = 0; j <= i; ++j) pair[i][j] = 0; } // type each exon for (var e = 0; e < exons.length; ++e) { //for (var e = 1; e < 3; ++e) { if (exons[e] == null) continue; var ee = exons[e]; // find good contigs and alleles that have good matches var ch = {}, gh = {}; for (var i = 0; i < ee.length; ++i) { if (elist[ee[i][1]][e] != null) ch[ee[i][0]] = true, gh[ee[i][1]] = true; } var ca = [], ga = []; for (var c in ch) ca.push(parseInt(c)); for (var g in gh) ga.push(parseInt(g)); var named_ca = []; for (var i = 0; i < ca.length; ++i) named_ca.push(clist[ca[i]]); warn("Processing exon "+(e+1)+" (" +ga.length+ " genes; " +ca.length+ " contigs: [" +named_ca.join(",")+ "])..."); // convert representation again var sc = []; for (var i = 0; i < ee.length; ++i) { var c = ee[i][0], g = ee[i][1]; if (sc[g] == null) sc[g] = []; if (sc[g][c] == null) sc[g][c] = 0xffff; sc[g][c] = sc[g][c] < ee[i][2]? sc[g][c] : ee[i][2]; } // set unmapped entries to high mismatch for (var i = 0; i < ga.length; ++i) for (var j = 0; j < ca.length; ++j) { var g = ga[i], c = ca[j]; if (sc[g][c] == null) sc[g][c] = 0xff; } // drop mismapped contigs var dropped = []; for (var c = 0; c < ca.length; ++c) { var min = 0x7fffffff, cc = ca[c]; for (var g = 0; g < ga.length; ++g) { var gg = ga[g]; min = min < sc[gg][cc]? min : sc[gg][cc]; } dropped[cc] = min > drop_thres? true : false; if (dropped[cc]) warn("Dropped contig " +clist[cc]+ " due to high divergence to all genes (minNM=" +min+ ")"); } // fill the pair array var min_nm = 0xffff; for (var i = 0; i < ga.length; ++i) { var gi = ga[i], g1 = sc[gi]; for (var j = i; j < ga.length; ++j) { var gj = ga[j], g2 = sc[gj], m = 0; for (var k = 0; k < ca.length; ++k) { c = ca[k]; if (!dropped[c]) m += g1[c] < g2[c]? g1[c] : g2[c]; } var x = m<<20 | 1<<6 | pri_exon[e]; if (gi < gj) pair[gj][gi] += x; else pair[gi][gj] += x; min_nm = min_nm < m? min_nm : m; } } } // genotyping var min_nm = 0x7fffffff; for (var i = 0; i < glist.length; ++i) for (var j = 0; j <= i; ++j) if ((pair[i][j]&63) == n_pri_exons) min_nm = min_nm < pair[i][j]>>20? min_nm : pair[i][j]>>20; var out = []; for (var i = 0; i < glist.length; ++i) for (var j = 0; j <= i; ++j) if ((pair[i][j]&63) == n_pri_exons && pair[i][j]>>20 <= min_nm + fuzzy) out.push([pair[i][j]>>20, pair[i][j]>>6&63, i, j]); out.sort(function(a, b) { return a[0]!=b[0]? a[0]-b[0] : b[1]-a[1]}); for (var i = 0; i < out.length; ++i) print(glist[out[i][2]], glist[out[i][3]], out[i][0], out[i][1]);