@gmod/bam 8.5.1 → 8.6.0

package/esm/htsget.d.ts

@@ -1,5 +1,5 @@
 import BamFile from './bamFile.ts';
-import type { BamRecordClass, BamRecordLike } from './bamFile.ts';
+import type { BamRecordClass, BamRecordLike, ReferenceSequenceFetcher } from './bamFile.ts';
 import type BamRecord from './record.ts';
 import type { BamOpts, BaseOpts } from './util.ts';
 import type { Fetcher } from 'generic-filehandle2';
@@ -33,6 +33,13 @@ export default class HtsgetFile<T extends BamRecordLike = BamRecord> extends Bam
         maxCacheBytes?: number;
         /** see {@link maxCacheBytes}: inherited, and inert in htsget mode */
         cacheIdleTimeoutMs?: number;
+        /**
+         * Reference bases for reads with no `MD` tag — see {@link BamFile}'s option
+         * of the same name. Unlike the cache options this one is live here: an
+         * htsget query resolves its reads' mismatches exactly as an indexed one
+         * does.
+         */
+        fetchReferenceSequence?: ReferenceSequenceFetcher;
     });
     /**
      * Requests a ticket and returns its data blocks decompressed and

package/esm/htsget.js

@@ -75,6 +75,7 @@ export default class HtsgetFile extends BamFile {
             recordClass: args.recordClass,
             maxCacheBytes: args.maxCacheBytes,
             cacheIdleTimeoutMs: args.cacheIdleTimeoutMs,
+            fetchReferenceSequence: args.fetchReferenceSequence,
         });
         this.baseUrl = args.baseUrl;
         this.trackId = args.trackId;
@@ -101,7 +102,9 @@ export default class HtsgetFile extends BamFile {
         const uncba = await this.fetchTicket(`referenceName=${chr}&start=${min}&end=${max}&format=BAM`, opts);
         const zero = new VirtualOffset(0, 0);
         const records = this.readBamFeatures(uncba.subarray(recordsOffset(uncba)), [], [], new Chunk(zero, zero, 0));
-        return appendInRange(records, chrId, min, max);
+        const result = appendInRange(records, chrId, min, max);
+        await this._applyReferenceSequence(result, chrId, chr, opts);
+        return result;
     }
     async getHeaderPre(opts = {}) {
         // format is the only parameter the spec permits alongside class=header;

package/esm/htsget.js.map

@@ -1 +1 @@
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+{"version":3,"file":"htsget.js","sourceRoot":"","sources":["../src/htsget.ts"],"names":[],"mappings":"AAAA,OAAO,EAAE,KAAK,EAAE,MAAM,uBAAuB,CAAA;AAE7C,OAAO,OAAO,EAAE,EAAE,SAAS,EAAE,MAAM,cAAc,CAAA;AACjD,OAAO,KAAK,MAAM,YAAY,CAAA;AAC9B,OAAO,EAAE,aAAa,EAAE,gBAAgB,EAAE,YAAY,EAAE,MAAM,WAAW,CAAA;AACzE,OAAO,EAAE,aAAa,EAAE,MAAM,oBAAoB,CAAA;AA2BlD,kEAAkE;AAClE,+EAA+E;AAC/E,iFAAiF;AACjF,SAAS,kBAAkB,CAAC,IAAY;IACtC,IAAI,MAAmC,CAAA;IACvC,IAAI,CAAC;QACH,MAAM,GAAG,IAAI,CAAC,KAAK,CAAC,IAAI,CAAC,CAAA;IAC3B,CAAC;IAAC,MAAM,CAAC;QACP,yCAAyC;IAC3C,CAAC;IACD,MAAM,GAAG,GAAG,MAAM,EAAE,MAAM,CAAA;IAC1B,OAAO,GAAG,EAAE,KAAK,KAAK,SAAS;QAC7B,CAAC,CAAC,IAAI;QACN,CAAC,CAAC,GAAG,CAAC,OAAO,KAAK,SAAS;YACzB,CAAC,CAAC,GAAG,CAAC,KAAK;YACX,CAAC,CAAC,GAAG,GAAG,CAAC,KAAK,KAAK,GAAG,CAAC,OAAO,EAAE,CAAA;AACtC,CAAC;AAED;;;;;;;;;;;GAWG;AACH,SAAS,aAAa,CAAC,KAAiB;IACtC,MAAM,QAAQ,GAAG,IAAI,QAAQ,CAC3B,KAAK,CAAC,MAAM,EACZ,KAAK,CAAC,UAAU,EAChB,KAAK,CAAC,UAAU,CACjB,CAAA;IACD,IAAI,KAAK,CAAC,UAAU,GAAG,CAAC,IAAI,QAAQ,CAAC,QAAQ,CAAC,CAAC,EAAE,IAAI,CAAC,KAAK,SAAS,EAAE,CAAC;QACrE,OAAO,CAAC,CAAA;IACV,CAAC;IACD,MAAM,IAAI,GAAG,YAAY,CAAC,KAAK,EAAE,CAAC,GAAG,QAAQ,CAAC,QAAQ,CAAC,CAAC,EAAE,IAAI,CAAC,EAAE,CAAC,CAAC,EAAE,CAAC,CAAC,CAAC,CAAA;IACxE,IAAI,CAAC,IAAI,EAAE,CAAC;QACV,MAAM,IAAI,KAAK,CAAC,yCAAyC,CAAC,CAAA;IAC5D,CAAC;IACD,OAAO,IAAI,CAAC,GAAG,CAAA;AACjB,CAAC;AAED,KAAK,UAAU,OAAO,CAAC,OAAgB,EAAE,GAAW,EAAE,IAAkB;IACtE,MAAM,GAAG,GAAG,MAAM,OAAO,CAAC,GAAG,EAAE,IAAI,CAAC,CAAA;IACpC,IAAI,CAAC,GAAG,CAAC,EAAE,EAAE,CAAC;QACZ,MAAM,IAAI,KAAK,CACb,QAAQ,GAAG,CAAC,MAAM,aAAa,GAAG,KAAK,kBAAkB,CAAC,MAAM,GAAG,CAAC,IAAI,EAAE,CAAC,EAAE,CAC9E,CAAA;IACH,CAAC;IACD,OAAO,GAAG,CAAA;AACZ,CAAC;AAED,KAAK,UAAU,UAAU,CACvB,OAAgB,EAChB,EAAE,GAAG,EAAE,OAAO,EAAe,EAC7B,IAAkB;IAElB,0EAA0E;IAC1E,uDAAuD;IACvD,+CAA+C;IAC/C,MAAM,EAAE,OAAO,EAAE,QAAQ,EAAE,GAAG,IAAI,EAAE,GAAG,OAAO,IAAI,EAAE,CAAA;IACpD,MAAM,GAAG,GAAG,GAAG,CAAC,UAAU,CAAC,OAAO,CAAC;QACjC,CAAC,CAAC,MAAM,OAAO,CAAC,OAAO,EAAE,GAAG,CAAC;QAC7B,CAAC,CAAC,MAAM,OAAO,CAAC,OAAO,EAAE,GAAG,EAAE,EAAE,GAAG,IAAI,EAAE,OAAO,EAAE,IAAI,EAAE,CAAC,CAAA;IAC3D,OAAO,IAAI,UAAU,CAAC,MAAM,GAAG,CAAC,WAAW,EAAE,CAAC,CAAA;AAChD,CAAC;AAED,KAAK,UAAU,cAAc,CAC3B,OAAgB,EAChB,GAAkB,EAClB,IAAkB;IAElB,2EAA2E;IAC3E,OAAO,gBAAgB,CACrB,MAAM,OAAO,CAAC,GAAG,CACf,GAAG,CAAC,GAAG,CAAC,KAAK,EAAC,CAAC,EAAC,EAAE,CAAC,KAAK,CAAC,MAAM,UAAU,CAAC,OAAO,EAAE,CAAC,EAAE,IAAI,CAAC,CAAC,CAAC,CAC9D,CACF,CAAA;AACH,CAAC;AAED,MAAM,CAAC,OAAO,OAAO,UAEnB,SAAQ,OAAU;IACV,OAAO,CAAQ;IAEf,OAAO,CAAQ;IAEf,OAAO,CAAS;IAExB,YAAY,IAiCX;QACC,KAAK,CAAC;YACJ,MAAM,EAAE,IAAI;YACZ,WAAW,EAAE,IAAI,CAAC,WAAW;YAC7B,aAAa,EAAE,IAAI,CAAC,aAAa;YACjC,kBAAkB,EAAE,IAAI,CAAC,kBAAkB;YAC3C,sBAAsB,EAAE,IAAI,CAAC,sBAAsB;SACpD,CAAC,CAAA;QACF,IAAI,CAAC,OAAO,GAAG,IAAI,CAAC,OAAO,CAAA;QAC3B,IAAI,CAAC,OAAO,GAAG,IAAI,CAAC,OAAO,CAAA;QAC3B,IAAI,CAAC,OAAO,GAAG,IAAI,CAAC,KAAK,IAAI,CAAC,CAAC,KAAK,EAAE,IAAI,EAAE,EAAE,CAAC,KAAK,CAAC,KAAK,EAAE,IAAI,CAAC,CAAC,CAAA;IACpE,CAAC;IAED;;;OAGG;IACK,KAAK,CAAC,WAAW,CAAC,KAAa,EAAE,IAAe;QACtD,MAAM,GAAG,GAAG,GAAG,IAAI,CAAC,OAAO,IAAI,IAAI,CAAC,OAAO,IAAI,KAAK,EAAE,CAAA;QACtD,MAAM,GAAG,GAAG,MAAM,OAAO,CAAC,IAAI,CAAC,OAAO,EAAE,GAAG,EAAE,EAAE,MAAM,EAAE,IAAI,EAAE,MAAM,EAAE,CAAC,CAAA;QACtE,MAAM,MAAM,GAAiB,MAAM,GAAG,CAAC,IAAI,EAAE,CAAA;QAC7C,OAAO,cAAc,CAAC,IAAI,CAAC,OAAO,EAAE,MAAM,CAAC,MAAM,CAAC,IAAI,EAAE;YACtD,MAAM,EAAE,IAAI,EAAE,MAAM;SACrB,CAAC,CAAA;IACJ,CAAC;IAED,KAAK,CAAC,kBAAkB,CACtB,GAAW,EACX,GAAW,EACX,GAAW,EACX,IAAc;QAEd,MAAM,IAAI,CAAC,SAAS,CAAC,IAAI,CAAC,CAAA;QAC1B,MAAM,KAAK,GAAG,IAAI,CAAC,UAAU,EAAE,CAAC,GAAG,CAAC,CAAA;QACpC,IAAI,KAAK,KAAK,SAAS,EAAE,CAAC;YACxB,OAAO,EAAE,CAAA;QACX,CAAC;QACD,MAAM,KAAK,GAAG,MAAM,IAAI,CAAC,WAAW,CAClC,iBAAiB,GAAG,UAAU,GAAG,QAAQ,GAAG,aAAa,EACzD,IAAI,CACL,CAAA;QACD,MAAM,IAAI,GAAG,IAAI,aAAa,CAAC,CAAC,EAAE,CAAC,CAAC,CAAA;QACpC,MAAM,OAAO,GAAG,IAAI,CAAC,eAAe,CAClC,KAAK,CAAC,QAAQ,CAAC,aAAa,CAAC,KAAK,CAAC,CAAC,EACpC,EAAE,EACF,EAAE,EACF,IAAI,KAAK,CAAC,IAAI,EAAE,IAAI,EAAE,CAAC,CAAC,CACzB,CAAA;QACD,MAAM,MAAM,GAAG,aAAa,CAAC,OAAO,EAAE,KAAK,EAAE,GAAG,EAAE,GAAG,CAAC,CAAA;QACtD,MAAM,IAAI,CAAC,uBAAuB,CAAC,MAAM,EAAE,KAAK,EAAE,GAAG,EAAE,IAAI,CAAC,CAAA;QAC5D,OAAO,MAAM,CAAA;IACf,CAAC;IAED,KAAK,CAAC,YAAY,CAAC,OAAiB,EAAE;QACpC,wEAAwE;QACxE,wDAAwD;QACxD,MAAM,KAAK,GAAG,MAAM,IAAI,CAAC,WAAW,CAAC,yBAAyB,EAAE,IAAI,CAAC,CAAA;QACrE,MAAM,SAAS,GAAG,IAAI,CAAC,WAAW,CAAC,KAAK,CAAC,CAAA;QACzC,IAAI,CAAC,SAAS,EAAE,CAAC;YACf,MAAM,IAAI,KAAK,CAAC,2CAA2C,CAAC,CAAA;QAC9D,CAAC;QACD,OAAO,SAAS,CAAA;IAClB,CAAC;CACF"}

package/esm/index.d.ts

@@ -3,8 +3,12 @@ export { DEFAULT_CACHE_IDLE_TIMEOUT_MS, DEFAULT_MAX_CACHE_BYTES, default as BamF
 export { default as CSI } from './csi.ts';
 export { default as BamRecord } from './record.ts';
 export { default as HtsgetFile } from './htsget.ts';
+export { MISMATCH_DELETION, MISMATCH_HARD_CLIP, MISMATCH_INSERTION, MISMATCH_REF_SKIP, MISMATCH_SOFT_CLIP, MISMATCH_SUBST, forEachMismatchNumeric, } from './mismatches.ts';
+export { packReference } from './reference.ts';
 export type { NumericCigar } from './record.ts';
-export type { BamRecordClass, BamRecordLike } from './bamFile.ts';
+export type { BamRecordClass, BamRecordLike, ReferenceSequenceFetcher, } from './bamFile.ts';
+export type { Mismatch, MismatchCallback, MismatchOptions, } from './mismatches.ts';
+export type { PackedReference } from './reference.ts';
 export type { BamOpts, BaseOpts } from './util.ts';
 export type { IndexCovEntry } from './bai.ts';
 export type { Fetcher } from 'generic-filehandle2';

package/esm/index.js

@@ -3,4 +3,10 @@ export { DEFAULT_CACHE_IDLE_TIMEOUT_MS, DEFAULT_MAX_CACHE_BYTES, default as BamF
 export { default as CSI } from "./csi.js";
 export { default as BamRecord } from "./record.js";
 export { default as HtsgetFile } from "./htsget.js";
+// The mismatch walk, and the codes it reports differences as. The walk is
+// exported alongside `record.forEachMismatch` for callers holding BAM's packed
+// arrays without a record around them — a SAM parser, or a worker that was
+// posted the typed arrays.
+export { MISMATCH_DELETION, MISMATCH_HARD_CLIP, MISMATCH_INSERTION, MISMATCH_REF_SKIP, MISMATCH_SOFT_CLIP, MISMATCH_SUBST, forEachMismatchNumeric, } from "./mismatches.js";
+export { packReference } from "./reference.js";
 //# sourceMappingURL=index.js.map

package/esm/index.js.map

@@ -1 +1 @@
-{"version":3,"file":"index.js","sourceRoot":"","sources":["../src/index.ts"],"names":[],"mappings":"AAAA,OAAO,EAAE,OAAO,IAAI,GAAG,EAAE,MAAM,UAAU,CAAA;AACzC,OAAO,EACL,6BAA6B,EAC7B,uBAAuB,EACvB,OAAO,IAAI,OAAO,GACnB,MAAM,cAAc,CAAA;AACrB,OAAO,EAAE,OAAO,IAAI,GAAG,EAAE,MAAM,UAAU,CAAA;AACzC,OAAO,EAAE,OAAO,IAAI,SAAS,EAAE,MAAM,aAAa,CAAA;AAClD,OAAO,EAAE,OAAO,IAAI,UAAU,EAAE,MAAM,aAAa,CAAA"}
+{"version":3,"file":"index.js","sourceRoot":"","sources":["../src/index.ts"],"names":[],"mappings":"AAAA,OAAO,EAAE,OAAO,IAAI,GAAG,EAAE,MAAM,UAAU,CAAA;AACzC,OAAO,EACL,6BAA6B,EAC7B,uBAAuB,EACvB,OAAO,IAAI,OAAO,GACnB,MAAM,cAAc,CAAA;AACrB,OAAO,EAAE,OAAO,IAAI,GAAG,EAAE,MAAM,UAAU,CAAA;AACzC,OAAO,EAAE,OAAO,IAAI,SAAS,EAAE,MAAM,aAAa,CAAA;AAClD,OAAO,EAAE,OAAO,IAAI,UAAU,EAAE,MAAM,aAAa,CAAA;AAEnD,0EAA0E;AAC1E,+EAA+E;AAC/E,2EAA2E;AAC3E,2BAA2B;AAC3B,OAAO,EACL,iBAAiB,EACjB,kBAAkB,EAClB,kBAAkB,EAClB,iBAAiB,EACjB,kBAAkB,EAClB,cAAc,EACd,sBAAsB,GACvB,MAAM,iBAAiB,CAAA;AACxB,OAAO,EAAE,aAAa,EAAE,MAAM,gBAAgB,CAAA"}

package/esm/mismatches.d.ts

@@ -0,0 +1,114 @@
+import type { PackedReference } from './reference.ts';
+/**
+ * The kind of difference a {@link Mismatch} reports, as the CIGAR-style char
+ * code it corresponds to. `@gmod/cram`'s `forEachMismatch` emits the same
+ * values (its `RF_*` constants), so one `switch` handles records from either
+ * format.
+ *
+ * Note these are char codes and NOT the packed-CIGAR op numbers in `cigar.ts`
+ * — `MISMATCH_DELETION` is 68 (`'D'`), where `CIGAR_DEL` is 2.
+ */
+export declare const MISMATCH_SUBST = 88;
+export declare const MISMATCH_INSERTION = 73;
+export declare const MISMATCH_DELETION = 68;
+export declare const MISMATCH_REF_SKIP = 78;
+export declare const MISMATCH_SOFT_CLIP = 83;
+export declare const MISMATCH_HARD_CLIP = 72;
+/**
+ * One difference between a read and the reference, as
+ * {@link BamRecord.getMismatches} reports it.
+ *
+ * This is the level most consumers want. Deriving the same thing from `CIGAR`
+ * and `MD` yourself means knowing that MD counts reference bases and the CIGAR
+ * counts both, that MD is absent from a majority of aligners' output and the
+ * reference has to stand in for it, that an `=`/`X` CIGAR carries the
+ * substitutions itself, and that a deletion's MD payload has to be stepped over
+ * rather than read as matches. Every one of those has been a bug in a
+ * downstream consumer.
+ */
+export interface Mismatch {
+    /**
+     * Which kind of difference: `MISMATCH_SUBST` (X), `MISMATCH_INSERTION` (I),
+     * `MISMATCH_DELETION` (D), `MISMATCH_REF_SKIP` (N), `MISMATCH_SOFT_CLIP` (S)
+     * or `MISMATCH_HARD_CLIP` (H). A substitution arrives as `MISMATCH_SUBST`
+     * whether the file spelled it with MD, with an `X` CIGAR op, or not at all
+     * (leaving it to be found against the reference).
+     */
+    code: number;
+    /** 0-based reference position the difference starts at */
+    refPos: number;
+    /**
+     * How many reference bases it covers: 1 for a substitution, the deleted or
+     * skipped length for D/N, and 0 for insertions and clips, which consume read
+     * bases without consuming reference.
+     */
+    length: number;
+    /**
+     * The substituted base for X, or the inserted bases for I; empty for
+     * D/N/S/H, which have no bases of their own to report. Also empty for an
+     * insertion in a read with no stored sequence (`SEQ` of `*`), where the
+     * length is all the file kept.
+     */
+    bases: string;
+    /** quality score of a substituted base, or -1 when the read stores none */
+    qual: number;
+    /**
+     * Char code of the reference base a substitution replaces, 0 when unknown —
+     * which is what an `X` CIGAR op in a read carrying neither an MD tag nor a
+     * reference gives. Upper-cased, since a soft-masked reference would otherwise
+     * report lowercase.
+     */
+    refBaseCode: number;
+    /** read bases consumed: the inserted or clipped length; 0 otherwise */
+    clipLength: number;
+}
+export type MismatchCallback = (code: number, refPos: number, length: number, bases: string, qual: number, refBaseCode: number, clipLength: number) => void;
+export interface MismatchOptions {
+    /**
+     * Only report differences touching this reference range, 0-based and
+     * half-open like every other range this library takes. A deletion or skip is
+     * reported when any of the bases it covers falls in the range; everything
+     * else when its own position does.
+     *
+     * (`@gmod/cram`'s equivalent option is **closed** at `end` — a known wart
+     * over there, tracked in its TODO.md. Half-open is the one to write new code
+     * against.)
+     */
+    start?: number;
+    end?: number;
+    /**
+     * Reference bases to resolve substitutions against, for reads with no MD tag.
+     * Overrides whatever {@link BamRecord.setReference} bound, and unlike that
+     * method it takes a region of any extent: bases outside it are simply left
+     * uncompared. Pack it once per region with `packReference`, not per read.
+     */
+    ref?: PackedReference;
+}
+/**
+ * The mismatch walk over a record's already-packed fields, for callers holding
+ * BAM's arrays without a {@link BamRecord} around them — a SAM parser, or a
+ * worker that was handed the typed arrays rather than the record.
+ * `record.forEachMismatch()` is this function with the record's own fields
+ * filled in, and is what most code should call.
+ *
+ * Nothing here allocates per difference except the `bases` string, and that
+ * only for substitutions and insertions.
+ *
+ * @param cigar packed CIGAR ops, i.e. `record.NUMERIC_CIGAR`
+ * @param numericSeq 4-bit packed SEQ, i.e. `record.NUMERIC_SEQ`
+ * @param seqLength bases in `numericSeq`; 0 for a read stored with `SEQ` of `*`
+ * @param md the MD tag's bytes (`record.NUMERIC_MD`), or undefined. Preferred
+ *   over `ref` when present, being both cheaper and what the aligner asserted
+ * @param qual per-base quality scores, or null/undefined when the read has none
+ * @param ref reference bases to compare against when there is no MD tag. Bases
+ *   the region does not cover are left uncompared
+ * @param refStart the record's own 0-based start, which every reported position
+ *   is relative to
+ * @param windowStart 0-based half-open reference window to report within. Pass
+ *   `-Infinity`/`Infinity` for the whole read; a viewport that clips the walk
+ *   is what keeps a chromosome-spanning contig alignment from being walked in
+ *   full for every screenful
+ * @param windowEnd
+ * @param callback `(code, refPos, length, bases, qual, refBaseCode, clipLength)`
+ */
+export declare function forEachMismatchNumeric(cigar: ArrayLike<number>, numericSeq: ArrayLike<number>, seqLength: number, md: ArrayLike<number> | undefined, qual: ArrayLike<number> | null | undefined, ref: PackedReference | undefined, refStart: number, windowStart: number, windowEnd: number, callback: MismatchCallback): void;

package/esm/mismatches.js

@@ -0,0 +1,393 @@
+import { CIGAR_DEL, CIGAR_DIFF, CIGAR_EQUAL, CIGAR_HARD_CLIP, CIGAR_INS, CIGAR_MATCH, CIGAR_REF_SKIP, CIGAR_SOFT_CLIP, } from "./cigar.js";
+import { CHAR_CODE_FROM_NIBBLE, referenceNibble } from "./reference.js";
+import { SEQRET_DECODER } from "./seqAlphabet.js";
+/**
+ * The kind of difference a {@link Mismatch} reports, as the CIGAR-style char
+ * code it corresponds to. `@gmod/cram`'s `forEachMismatch` emits the same
+ * values (its `RF_*` constants), so one `switch` handles records from either
+ * format.
+ *
+ * Note these are char codes and NOT the packed-CIGAR op numbers in `cigar.ts`
+ * — `MISMATCH_DELETION` is 68 (`'D'`), where `CIGAR_DEL` is 2.
+ */
+export const MISMATCH_SUBST = 88; // 'X'
+export const MISMATCH_INSERTION = 73; // 'I'
+export const MISMATCH_DELETION = 68; // 'D'
+export const MISMATCH_REF_SKIP = 78; // 'N'
+export const MISMATCH_SOFT_CLIP = 83; // 'S'
+export const MISMATCH_HARD_CLIP = 72; // 'H'
+// M and = both mean "aligned to the reference", differing only in whether the
+// file promises the bases match. Which is exactly the distinction MD (or the
+// reference) exists to settle, so the walk treats them identically.
+const CIGAR_M_EQ_MASK = (1 << CIGAR_MATCH) | (1 << CIGAR_EQUAL);
+// A clip has no bases to report — its length travels in `clipLength`, which is
+// what every consumer reads.
+const NO_BASES = '';
+function reportRefMismatch(callback, refPos, seqNibble, qual, refNibble) {
+    callback(MISMATCH_SUBST, refPos, 1, SEQRET_DECODER[seqNibble], qual, CHAR_CODE_FROM_NIBBLE[refNibble], 0);
+}
+// One base compared on its own: the ends of a run whose length or alignment
+// leaves it without a partner in the same byte.
+function compareRefBase(callback, numericSeq, qual, ref, seqIdx, refIdx, refPos) {
+    const seqNibble = (numericSeq[seqIdx >> 1] >> ((1 - (seqIdx & 1)) << 2)) & 0xf;
+    const refNibble = referenceNibble(ref, refIdx);
+    if (seqNibble !== refNibble) {
+        reportRefMismatch(callback, refPos, seqNibble, qual ? qual[seqIdx] : -1, refNibble);
+    }
+}
+/**
+ * The mismatch walk over a record's already-packed fields, for callers holding
+ * BAM's arrays without a {@link BamRecord} around them — a SAM parser, or a
+ * worker that was handed the typed arrays rather than the record.
+ * `record.forEachMismatch()` is this function with the record's own fields
+ * filled in, and is what most code should call.
+ *
+ * Nothing here allocates per difference except the `bases` string, and that
+ * only for substitutions and insertions.
+ *
+ * @param cigar packed CIGAR ops, i.e. `record.NUMERIC_CIGAR`
+ * @param numericSeq 4-bit packed SEQ, i.e. `record.NUMERIC_SEQ`
+ * @param seqLength bases in `numericSeq`; 0 for a read stored with `SEQ` of `*`
+ * @param md the MD tag's bytes (`record.NUMERIC_MD`), or undefined. Preferred
+ *   over `ref` when present, being both cheaper and what the aligner asserted
+ * @param qual per-base quality scores, or null/undefined when the read has none
+ * @param ref reference bases to compare against when there is no MD tag. Bases
+ *   the region does not cover are left uncompared
+ * @param refStart the record's own 0-based start, which every reported position
+ *   is relative to
+ * @param windowStart 0-based half-open reference window to report within. Pass
+ *   `-Infinity`/`Infinity` for the whole read; a viewport that clips the walk
+ *   is what keeps a chromosome-spanning contig alignment from being walked in
+ *   full for every screenful
+ * @param windowEnd
+ * @param callback `(code, refPos, length, bases, qual, refBaseCode, clipLength)`
+ */
+export function forEachMismatchNumeric(cigar, numericSeq, seqLength, md, qual, ref, refStart, windowStart, windowEnd, callback) {
+    // The walk runs in read-relative offsets — `roffset` reference bases and
+    // `soffset` read bases consumed — and converts back at the callback, so the
+    // window is converted once here rather than per op.
+    //
+    // Clamped to int32 rather than left at the ±Infinity an unwindowed walk
+    // passes, because every op of the walk compares an offset against these and
+    // Infinity makes each of those a Float64 comparison. BAM positions are int32,
+    // so this cannot narrow a window anyone can express.
+    const winLo = windowStart <= -0x80000000 ? -0x80000000 : windowStart - refStart;
+    const winHi = windowEnd >= 0x7fffffff ? 0x7fffffff : windowEnd - refStart;
+    // Fast path for reads with no sequence (e.g. secondary alignments with SEQ='*')
+    if (seqLength === 0) {
+        let roffset = 0;
+        for (let i = 0, l = cigar.length; i < l; i++) {
+            // `roffset` only grows, and nothing at or past the window's right edge is
+            // reported, so the rest of the CIGAR cannot produce anything (see the
+            // same check in the main loop)
+            if (roffset >= winHi) {
+                break;
+            }
+            const packed = cigar[i];
+            const len = packed >>> 4;
+            const op = packed & 0xf;
+            // X consumes the reference exactly like M/=; without a sequence there are
+            // no bases to report for it, but it still has to advance — leaving it out
+            // shifted every later op left by the total X length, which is every indel
+            // in an --eqx CIGAR walked without a sequence.
+            if ((1 << op) & CIGAR_M_EQ_MASK || op === CIGAR_DIFF) {
+                roffset += len;
+            }
+            else if (op === CIGAR_INS) {
+                if (roffset >= winLo && roffset < winHi) {
+                    callback(MISMATCH_INSERTION, refStart + roffset, 0, '', -1, 0, len);
+                }
+            }
+            else if (op === CIGAR_DEL) {
+                if (roffset < winHi && roffset + len > winLo) {
+                    callback(MISMATCH_DELETION, refStart + roffset, len, NO_BASES, -1, 0, 0);
+                }
+                roffset += len;
+            }
+            else if (op === CIGAR_REF_SKIP) {
+                if (roffset < winHi && roffset + len > winLo) {
+                    callback(MISMATCH_REF_SKIP, refStart + roffset, len, NO_BASES, -1, 0, 0);
+                }
+                roffset += len;
+            }
+            else if (op === CIGAR_SOFT_CLIP) {
+                if (roffset >= winLo && roffset < winHi) {
+                    callback(MISMATCH_SOFT_CLIP, refStart + roffset, 0, NO_BASES, -1, 0, len);
+                }
+            }
+            else if (op === CIGAR_HARD_CLIP) {
+                if (roffset >= winLo && roffset < winHi) {
+                    callback(MISMATCH_HARD_CLIP, refStart + roffset, 0, NO_BASES, -1, 0, len);
+                }
+            }
+        }
+        return;
+    }
+    const mdLength = md?.length ?? 0;
+    const hasQual = !!qual;
+    const hasMD = md && mdLength > 0;
+    // Where the reference region sits in read-relative offsets, and the window
+    // narrowed to it. Only base COMPARISON is bounded by the region — an indel or
+    // a clip needs no reference base, so a region covering part of a read still
+    // reports every one of them.
+    //
+    // Ternaries rather than Math.max/Math.min, which matters more than it looks:
+    // an unwindowed walk has `winLo`/`winHi` at ±Infinity, so Math.min would hand
+    // back a Float64 and `cmpHi` would carry that all the way into `jHi`, the
+    // bound of the innermost (two-bases-per-byte) loop. This way an unwindowed
+    // walk keeps that bound a Smi, which measured ~8% of the reference path on
+    // dense short reads.
+    let refOffset = 0;
+    let cmpLo = 0;
+    let cmpHi = 0;
+    if (ref !== undefined) {
+        refOffset = refStart - ref.start;
+        const refLo = -refOffset;
+        const refHi = ref.length - refOffset;
+        cmpLo = winLo > refLo ? winLo : refLo;
+        cmpHi = winHi < refHi ? winHi : refHi;
+    }
+    let roffset = 0;
+    let soffset = 0;
+    let mdIdx = 0;
+    let mdMatchRemaining = 0;
+    if (hasMD) {
+        while (mdIdx < mdLength) {
+            const c = md[mdIdx];
+            if (c >= 48 && c <= 57) {
+                mdMatchRemaining = mdMatchRemaining * 10 + (c - 48);
+                mdIdx++;
+            }
+            else {
+                break;
+            }
+        }
+    }
+    for (let i = 0, l = cigar.length; i < l; i++) {
+        // Stop at the window's right edge rather than walking the rest of the
+        // CIGAR: `roffset` only grows, and every report below needs
+        // `roffset < winHi`, so nothing past here can produce anything. Matters for
+        // a whole chromosome stored as one BAM read, whose CIGAR runs to millions
+        // of ops for a screenful of them — and costs one compare per op otherwise,
+        // since an unwindowed walk has `winHi` at +Infinity.
+        if (roffset >= winHi) {
+            break;
+        }
+        const packed = cigar[i];
+        const len = packed >>> 4;
+        const op = packed & 0xf;
+        if ((1 << op) & CIGAR_M_EQ_MASK) {
+            if (hasMD) {
+                let remaining = len;
+                let localOffset = 0;
+                while (remaining > 0) {
+                    if (mdMatchRemaining >= remaining) {
+                        mdMatchRemaining -= remaining;
+                        localOffset += remaining;
+                        remaining = 0;
+                    }
+                    else {
+                        localOffset += mdMatchRemaining;
+                        remaining -= mdMatchRemaining;
+                        mdMatchRemaining = 0;
+                        if (mdIdx < mdLength && md[mdIdx] >= 65 && md[mdIdx] <= 90) {
+                            const pos = roffset + localOffset;
+                            if (pos >= winLo && pos < winHi) {
+                                const seqIdx = soffset + localOffset;
+                                const sb = numericSeq[seqIdx >> 1];
+                                const nibble = (sb >> ((1 - (seqIdx & 1)) << 2)) & 0xf;
+                                callback(MISMATCH_SUBST, refStart + pos, 1, SEQRET_DECODER[nibble], hasQual ? qual[seqIdx] : -1, md[mdIdx], 0);
+                            }
+                            mdIdx++;
+                            localOffset++;
+                            remaining--;
+                            mdMatchRemaining = 0;
+                            while (mdIdx < mdLength) {
+                                const c = md[mdIdx];
+                                if (c >= 48 && c <= 57) {
+                                    mdMatchRemaining = mdMatchRemaining * 10 + (c - 48);
+                                    mdIdx++;
+                                }
+                                else {
+                                    break;
+                                }
+                            }
+                        }
+                        else {
+                            break;
+                        }
+                    }
+                }
+            }
+            else if (ref) {
+                // Only compare bases whose reference position falls in the window AND
+                // in the region. A whole-chromosome contig has M ops totalling ~250M
+                // bases; without this clip every one is compared (and `ref` would have
+                // to cover the whole chromosome).
+                const jLo = cmpLo > roffset ? cmpLo - roffset : 0;
+                const jHi = cmpHi < roffset + len ? cmpHi - roffset : len;
+                let j = jLo;
+                // A leading odd read index has no partner in its byte, so compare it
+                // alone and let the pair loop start on a byte boundary.
+                if (j < jHi && (soffset + j) & 1) {
+                    compareRefBase(callback, numericSeq, qual, ref, soffset + j, refOffset + roffset + j, refStart + roffset + j);
+                    j++;
+                }
+                // Two bases per byte load and compare. `even`/`odd` differ only in
+                // which reference parity they put on a byte boundary, so one of them
+                // always lines up with the read's packed sequence; the nibbles are
+                // unpacked only for the byte that actually differs.
+                const refIdx = refOffset + roffset + j;
+                const refPairs = refIdx & 1 ? ref.odd : ref.even;
+                let refByte = (refIdx + (refIdx & 1)) >> 1;
+                let seqByte = (soffset + j) >> 1;
+                for (; j + 1 < jHi; j += 2, refByte++, seqByte++) {
+                    const seqPair = numericSeq[seqByte];
+                    const refPair = refPairs[refByte];
+                    if (seqPair !== refPair) {
+                        const seqHi = (seqPair >> 4) & 0xf;
+                        const refHi = (refPair >> 4) & 0xf;
+                        if (seqHi !== refHi) {
+                            reportRefMismatch(callback, refStart + roffset + j, seqHi, hasQual ? qual[soffset + j] : -1, refHi);
+                        }
+                        const seqLo = seqPair & 0xf;
+                        const refLo = refPair & 0xf;
+                        if (seqLo !== refLo) {
+                            reportRefMismatch(callback, refStart + roffset + j + 1, seqLo, hasQual ? qual[soffset + j + 1] : -1, refLo);
+                        }
+                    }
+                }
+                if (j < jHi) {
+                    compareRefBase(callback, numericSeq, qual, ref, soffset + j, refOffset + roffset + j, refStart + roffset + j);
+                }
+            }
+            soffset += len;
+            roffset += len;
+        }
+        else if (op === CIGAR_INS) {
+            if (roffset >= winLo && roffset < winHi) {
+                // Optimized insertion base extraction - avoid string concat for common
+                // cases
+                let insertedBases;
+                if (len === 1) {
+                    // Single base insertion - most common case
+                    const sb = numericSeq[soffset >> 1];
+                    const nibble = (sb >> ((1 - (soffset & 1)) << 2)) & 0xf;
+                    insertedBases = SEQRET_DECODER[nibble];
+                }
+                else if (len === 2) {
+                    // Two base insertion - second most common
+                    const seqIdx0 = soffset;
+                    const sb0 = numericSeq[seqIdx0 >> 1];
+                    const nibble0 = (sb0 >> ((1 - (seqIdx0 & 1)) << 2)) & 0xf;
+                    const seqIdx1 = soffset + 1;
+                    const sb1 = numericSeq[seqIdx1 >> 1];
+                    const nibble1 = (sb1 >> ((1 - (seqIdx1 & 1)) << 2)) & 0xf;
+                    insertedBases = SEQRET_DECODER[nibble0] + SEQRET_DECODER[nibble1];
+                }
+                else {
+                    const bases = new Array(len);
+                    for (let j = 0; j < len; j++) {
+                        const seqIdx = soffset + j;
+                        const sb = numericSeq[seqIdx >> 1];
+                        const nibble = (sb >> ((1 - (seqIdx & 1)) << 2)) & 0xf;
+                        bases[j] = SEQRET_DECODER[nibble];
+                    }
+                    insertedBases = bases.join('');
+                }
+                callback(MISMATCH_INSERTION, refStart + roffset, 0, insertedBases, -1, 0, len);
+            }
+            soffset += len;
+        }
+        else if (op === CIGAR_DEL) {
+            if (roffset < winHi && roffset + len > winLo) {
+                callback(MISMATCH_DELETION, refStart + roffset, len, NO_BASES, -1, 0, 0);
+            }
+            // MD spells a deletion as ^ then the deleted reference bases, which are
+            // not a difference this reports (the D above already is) but do have to
+            // be stepped over, or every later position in the read reads off the
+            // wrong part of the tag.
+            // eslint-disable-next-line @typescript-eslint/no-confusing-non-null-assertion
+            if (hasMD && mdIdx < mdLength && md[mdIdx] === 94) {
+                mdIdx++;
+                while (mdIdx < mdLength && md[mdIdx] >= 65) {
+                    mdIdx++;
+                }
+                mdMatchRemaining = 0;
+                while (mdIdx < mdLength) {
+                    const c = md[mdIdx];
+                    if (c >= 48 && c <= 57) {
+                        mdMatchRemaining = mdMatchRemaining * 10 + (c - 48);
+                        mdIdx++;
+                    }
+                    else {
+                        break;
+                    }
+                }
+            }
+            roffset += len;
+        }
+        else if (op === CIGAR_REF_SKIP) {
+            if (roffset < winHi && roffset + len > winLo) {
+                callback(MISMATCH_REF_SKIP, refStart + roffset, len, NO_BASES, -1, 0, 0);
+            }
+            roffset += len;
+        }
+        else if (op === CIGAR_DIFF) {
+            for (let j = 0; j < len; j++) {
+                const seqIdx = soffset + j;
+                const sb = numericSeq[seqIdx >> 1];
+                const nibble = (sb >> ((1 - (seqIdx & 1)) << 2)) & 0xf;
+                // An X op says a substitution is here without saying what it replaces,
+                // so the reference base comes from MD or the region — and is 0, i.e.
+                // unknown, when the read carries neither.
+                let refBaseCode = 0;
+                if (hasMD) {
+                    if (mdMatchRemaining === 0 && mdIdx < mdLength && md[mdIdx] >= 65) {
+                        refBaseCode = md[mdIdx];
+                        mdIdx++;
+                        mdMatchRemaining = 0;
+                        while (mdIdx < mdLength) {
+                            const c = md[mdIdx];
+                            if (c >= 48 && c <= 57) {
+                                mdMatchRemaining = mdMatchRemaining * 10 + (c - 48);
+                                mdIdx++;
+                            }
+                            else {
+                                break;
+                            }
+                        }
+                    }
+                    else if (mdMatchRemaining > 0) {
+                        mdMatchRemaining--;
+                    }
+                }
+                else if (ref) {
+                    const refIdx = refOffset + roffset + j;
+                    if (refIdx >= 0 && refIdx < ref.length) {
+                        refBaseCode = CHAR_CODE_FROM_NIBBLE[referenceNibble(ref, refIdx)];
+                    }
+                }
+                const pos = roffset + j;
+                if (pos >= winLo && pos < winHi) {
+                    callback(MISMATCH_SUBST, refStart + pos, 1, SEQRET_DECODER[nibble], hasQual ? qual[seqIdx] : -1, refBaseCode, 0);
+                }
+            }
+            soffset += len;
+            roffset += len;
+        }
+        else if (op === CIGAR_SOFT_CLIP) {
+            if (roffset >= winLo && roffset < winHi) {
+                callback(MISMATCH_SOFT_CLIP, refStart + roffset, 0, NO_BASES, -1, 0, len);
+            }
+            soffset += len;
+        }
+        else if (op === CIGAR_HARD_CLIP) {
+            if (roffset >= winLo && roffset < winHi) {
+                callback(MISMATCH_HARD_CLIP, refStart + roffset, 0, NO_BASES, -1, 0, len);
+            }
+        }
+        // P (padding) consumes neither read nor reference and is not a difference
+    }
+}
+//# sourceMappingURL=mismatches.js.map

package/esm/mismatches.js.map

@@ -0,0 +1 @@
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