Illumina Complete Long Read presets (#1069)

* Implements a transition-aware alignment scoring scheme and configuration presets for ICLR

* Fix to enable use of general scoring matrix in ksw as suggested by lh3

---------

Co-authored-by: koadman <>

Author: koadman

README.md

@@ -139,12 +139,15 @@ parameters at the same time. The default setting is the same as `map-ont`.
 ```sh
 minimap2 -ax map-pb  ref.fa pacbio-reads.fq > aln.sam   # for PacBio CLR reads
 minimap2 -ax map-ont ref.fa ont-reads.fq > aln.sam      # for Oxford Nanopore reads
+minimap2 -ax map-iclr ref.fa iclr-reads.fq > aln.sam    # for Illumina Complete Long Reads
 ```
 The difference between `map-pb` and `map-ont` is that `map-pb` uses
 homopolymer-compressed (HPC) minimizers as seeds, while `map-ont` uses ordinary
-minimizers as seeds. Emperical evaluation suggests HPC minimizers improve
+minimizers as seeds. Empirical evaluation suggests HPC minimizers improve
 performance and sensitivity when aligning PacBio CLR reads, but hurt when aligning
-Nanopore reads.
+Nanopore reads. `map-iclr` uses an adjusted alignment scoring matrix that
+accounts for the low overall error rate in the reads, with transversion errors
+being less frequent than transitions.
 
 #### <a name="map-long-splice"></a>Map long mRNA/cDNA reads
 

align.c

@@ -21,6 +21,17 @@ static void ksw_gen_simple_mat(int m, int8_t *mat, int8_t a, int8_t b, int8_t sc
 		mat[(m - 1) * m + j] = sc_ambi;
 }
 
+static void ksw_gen_ts_mat(int m, int8_t *mat, int8_t a, int8_t b, int8_t transition, int8_t sc_ambi)
+{
+	assert(m==5);
+	ksw_gen_simple_mat(m,mat,a,b,sc_ambi);
+	transition = transition > 0? -transition : transition;
+	mat[0*m+2]=transition;  // A->G
+	mat[1*m+3]=transition;  // C->T
+	mat[2*m+0]=transition;  // G->A
+	mat[3*m+1]=transition;  // T->C
+}
+
 static inline void mm_seq_rev(uint32_t len, uint8_t *seq)
 {
 	uint32_t i;
@@ -323,6 +334,7 @@ static void mm_align_pair(void *km, const mm_mapopt_t *opt, int qlen, const uint
 		for (i = 0; i < qlen; ++i) fputc("ACGTN"[qseq[i]], stderr);
 		fputc('\n', stderr);
 	}
+	if (opt->b != opt->transition) flag |= KSW_EZ_GENERIC_SC;
 	if (opt->max_sw_mat > 0 && (int64_t)tlen * qlen > opt->max_sw_mat) {
 		ksw_reset_extz(ez);
 		ez->zdropped = 1;
@@ -586,7 +598,7 @@ static void mm_align1(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, int
 
 	r2->cnt = 0;
 	if (r->cnt == 0) return;
-	ksw_gen_simple_mat(5, mat, opt->a, opt->b, opt->sc_ambi);
+	ksw_gen_ts_mat(5, mat, opt->a, opt->b, opt->transition, opt->sc_ambi);
 	bw = (int)(opt->bw * 1.5 + 1.);
 	bw_long = (int)(opt->bw_long * 1.5 + 1.);
 	if (bw_long < bw) bw_long = bw;
@@ -844,7 +856,7 @@ static int mm_align1_inv(void *km, const mm_mapopt_t *opt, const mm_idx_t *mi, i
 	if (ql < opt->min_chain_score || ql > opt->max_gap) return 0;
 	if (tl < opt->min_chain_score || tl > opt->max_gap) return 0;
 
-	ksw_gen_simple_mat(5, mat, opt->a, opt->b, opt->sc_ambi);
+	ksw_gen_ts_mat(5, mat, opt->a, opt->b, opt->transition, opt->sc_ambi);
 	tseq = (uint8_t*)kmalloc(km, tl);
 	mm_idx_getseq(mi, r1->rid, r1->re, r2->rs, tseq);
 	qseq = r1->rev? &qseq0[0][r2->qe] : &qseq0[1][qlen - r2->qs];

main.c

@@ -120,7 +120,7 @@ static inline void yes_or_no(mm_mapopt_t *opt, int64_t flag, int long_idx, const
 
 int main(int argc, char *argv[])
 {
-	const char *opt_str = "2aSDw:k:K:t:r:f:Vv:g:G:I:d:XT:s:x:Hcp:M:n:z:A:B:O:E:m:N:Qu:R:hF:LC:yYPo:e:U:J:";
+	const char *opt_str = "2aSDw:k:K:t:r:f:Vv:g:G:I:d:XT:s:x:Hcp:M:n:z:A:B:b:O:E:m:N:Qu:R:hF:LC:yYPo:e:U:J:";
 	ketopt_t o = KETOPT_INIT;
 	mm_mapopt_t opt;
 	mm_idxopt_t ipt;
@@ -178,6 +178,7 @@ int main(int argc, char *argv[])
 		else if (c == 'm') opt.min_chain_score = atoi(o.arg);
 		else if (c == 'A') opt.a = atoi(o.arg);
 		else if (c == 'B') opt.b = atoi(o.arg);
+		else if (c == 'b') opt.transition = atoi(o.arg);
 		else if (c == 's') opt.min_dp_max = atoi(o.arg);
 		else if (c == 'C') opt.noncan = atoi(o.arg);
 		else if (c == 'I') ipt.batch_size = mm_parse_num(o.arg);
@@ -367,7 +368,7 @@ int main(int argc, char *argv[])
 		fprintf(fp_help, "    --version    show version number\n");
 		fprintf(fp_help, "  Preset:\n");
 		fprintf(fp_help, "    -x STR       preset (always applied before other options; see minimap2.1 for details) []\n");
-		fprintf(fp_help, "                 - map-pb/map-ont - PacBio CLR/Nanopore vs reference mapping\n");
+		fprintf(fp_help, "                 - map-pb/map-ont/map-iclr-prerender/map-iclr - PacBio/Nanopore/ICLR vs reference mapping\n");
 		fprintf(fp_help, "                 - map-hifi - PacBio HiFi reads vs reference mapping\n");
 		fprintf(fp_help, "                 - ava-pb/ava-ont - PacBio/Nanopore read overlap\n");
 		fprintf(fp_help, "                 - asm5/asm10/asm20 - asm-to-ref mapping, for ~0.1/1/5%% sequence divergence\n");

minimap.h

@@ -153,6 +153,7 @@ typedef struct {
 	float alt_drop;
 
 	int a, b, q, e, q2, e2; // matching score, mismatch, gap-open and gap-ext penalties
+	int transition; // transition mismatch score (A:G, C:T)
 	int sc_ambi; // score when one or both bases are "N"
 	int noncan;      // cost of non-canonical splicing sites
 	int junc_bonus;

options.c

@@ -45,6 +45,7 @@ void mm_mapopt_init(mm_mapopt_t *opt)
 	opt->alt_drop = 0.15f;
 
 	opt->a = 2, opt->b = 4, opt->q = 4, opt->e = 2, opt->q2 = 24, opt->e2 = 1;
+	opt->transition = opt->b;
 	opt->sc_ambi = 1;
 	opt->zdrop = 400, opt->zdrop_inv = 200;
 	opt->end_bonus = -1;
@@ -112,6 +113,14 @@ int mm_set_opt(const char *preset, mm_idxopt_t *io, mm_mapopt_t *mo)
 		mo->occ_dist = 500;
 		mo->min_mid_occ = 50, mo->max_mid_occ = 500;
 		mo->min_dp_max = 200;
+	} else if (strcmp(preset, "map-iclr-prerender") == 0) {
+		io->flag = 0, io->k = 15;
+		mo->b = 6, mo->transition = 1;
+		mo->q = 10, mo->q2 = 50;
+	} else if (strcmp(preset, "map-iclr") == 0) {
+		io->flag = 0, io->k = 19;
+		mo->b = 6, mo->transition = 4;
+		mo->q = 10, mo->q2 = 50;
 	} else if (strncmp(preset, "asm", 3) == 0) {
 		io->flag = 0, io->k = 19, io->w = 19;
 		mo->bw = 1000, mo->bw_long = 100000;