Alternative model for multiallelic and rare-variant calling. Proof-of-principle imple...

[samtools.git] / bcftools / call1.c

diff --git a/bcftools/call1.c b/bcftools/call1.c
index 3cc464949eb69e630ee7905c96d4f8050b1b569c..13f55332c9d0acf4712f485c4f55bc2575ffb7c4 100644 (file)
--- a/bcftools/call1.c
+++ b/bcftools/call1.c
@@ -33,13 +33,14 @@ KSTREAM_INIT(gzFile, gzread, 16384)
 #define VC_EM       0x10000
 #define VC_PAIRCALL 0x20000
 #define VC_QCNT     0x40000
+#define VC_INDEL_ONLY 0x80000
 
 typedef struct {
        int flag, prior_type, n1, n_sub, *sublist, n_perm;
        uint32_t *trio_aux;
        char *prior_file, **subsam, *fn_dict;
        uint8_t *ploidy;
-       double theta, pref, indel_frac, min_perm_p, min_smpl_frac, min_lrt;
+       double theta, pref, indel_frac, min_perm_p, min_smpl_frac, min_lrt, min_ma_lrt;
        void *bed;
 } viewconf_t;
 
@@ -283,6 +284,8 @@ static void write_header(bcf_hdr_t *h)
         kputs("##FORMAT=<ID=GL,Number=3,Type=Float,Description=\"Likelihoods for RR,RA,AA genotypes (R=ref,A=alt)\">\n", &str);
        if (!strstr(str.s, "##FORMAT=<ID=DP,"))
                kputs("##FORMAT=<ID=DP,Number=1,Type=Integer,Description=\"# high-quality bases\">\n", &str);
+       if (!strstr(str.s, "##FORMAT=<ID=DV,"))
+               kputs("##FORMAT=<ID=DV,Number=1,Type=Integer,Description=\"# high-quality non-reference bases\">\n", &str);
        if (!strstr(str.s, "##FORMAT=<ID=SP,"))
                kputs("##FORMAT=<ID=SP,Number=1,Type=Integer,Description=\"Phred-scaled strand bias P-value\">\n", &str);
        if (!strstr(str.s, "##FORMAT=<ID=PL,"))
@@ -316,9 +319,9 @@ int bcfview(int argc, char *argv[])
 
        tid = begin = end = -1;
        memset(&vc, 0, sizeof(viewconf_t));
-       vc.prior_type = vc.n1 = -1; vc.theta = 1e-3; vc.pref = 0.5; vc.indel_frac = -1.; vc.n_perm = 0; vc.min_perm_p = 0.01; vc.min_smpl_frac = 0; vc.min_lrt = 1;
+       vc.prior_type = vc.n1 = -1; vc.theta = 1e-3; vc.pref = 0.5; vc.indel_frac = -1.; vc.n_perm = 0; vc.min_perm_p = 0.01; vc.min_smpl_frac = 0; vc.min_lrt = 1; vc.min_ma_lrt = -1;
        memset(qcnt, 0, 8 * 256);
-       while ((c = getopt(argc, argv, "FN1:l:cC:eHAGvbSuP:t:p:QgLi:IMs:D:U:X:d:T:Y")) >= 0) {
+       while ((c = getopt(argc, argv, "FN1:l:cC:eHAGvbSuP:t:p:QgLi:IMs:D:U:X:d:T:Ywm:")) >= 0) {
                switch (c) {
                case '1': vc.n1 = atoi(optarg); break;
                case 'l': vc.bed = bed_read(optarg); break;
@@ -335,8 +338,10 @@ int bcfview(int argc, char *argv[])
                case 'u': vc.flag |= VC_UNCOMP | VC_BCFOUT; break;
                case 'g': vc.flag |= VC_CALL_GT | VC_CALL; break;
                case 'I': vc.flag |= VC_NO_INDEL; break;
+               case 'w': vc.flag |= VC_INDEL_ONLY; break;
                case 'M': vc.flag |= VC_ANNO_MAX; break;
                case 'Y': vc.flag |= VC_QCNT; break;
+        case 'm': vc.min_ma_lrt = atof(optarg); break;
                case 't': vc.theta = atof(optarg); break;
                case 'p': vc.pref = atof(optarg); break;
                case 'i': vc.indel_frac = atof(optarg); break;
@@ -392,6 +397,7 @@ int bcfview(int argc, char *argv[])
                fprintf(stderr, "       -g        call genotypes at variant sites (force -c)\n");
                fprintf(stderr, "       -i FLOAT  indel-to-substitution ratio [%.4g]\n", vc.indel_frac);
                fprintf(stderr, "       -I        skip indels\n");
+               fprintf(stderr, "       -m FLOAT  alternative model for multiallelic and rare-variant calling, include if P(chi^2)>=FLOAT\n");
                fprintf(stderr, "       -p FLOAT  variant if P(ref|D)<FLOAT [%.3g]\n", vc.pref);
                fprintf(stderr, "       -P STR    type of prior: full, cond2, flat [full]\n");
                fprintf(stderr, "       -t FLOAT  scaled substitution mutation rate [%.4g]\n", vc.theta);
@@ -482,6 +488,7 @@ int bcfview(int argc, char *argv[])
                if (vc.flag & VC_FIX_PL) bcf_fix_pl(b);
                is_indel = bcf_is_indel(b);
                if ((vc.flag & VC_NO_INDEL) && is_indel) continue;
+               if ((vc.flag & VC_INDEL_ONLY) && !is_indel) continue;
                if ((vc.flag & VC_ACGT_ONLY) && !is_indel) {
                        int x;
                        if (b->ref[0] == 0 || b->ref[1] != 0) continue;
@@ -515,7 +522,13 @@ int bcfview(int argc, char *argv[])
                        int i;
                        for (i = 0; i < 9; ++i) em[i] = -1.;
                }
-               if (vc.flag & VC_CALL) { // call variants
+        bcf_p1_set_ploidy(b, p1); // could be improved: do this per site to allow pseudo-autosomal regions
+        if ( !(vc.flag&VC_KEEPALT) && vc.flag&VC_CALL && vc.min_ma_lrt>=0 )
+        {
+            int gts = call_multiallelic_gt(b,p1,vc.min_ma_lrt);
+            if ( gts==0 && vc.flag & VC_VARONLY ) continue;
+        }
+               else if (vc.flag & VC_CALL) { // call variants
                        bcf_p1rst_t pr;
                        int calret = bcf_p1_cal(b, (em[7] >= 0 && em[7] < vc.min_lrt), p1, &pr);
                        if (n_processed % 100000 == 0) {