@gmod/bam 8.5.1 → 8.6.0

package/README.md

@@ -41,6 +41,36 @@ const records = (await bam.getRecordsForRange('chr1', 0, 100000)).filter(
 )
 ```
 
+## Mismatches
+
+`record.getMismatches()` gives every difference between a read and the reference
+— substitutions, insertions, deletions, reference skips and clips — without you
+having to interpret `CIGAR` and `MD` yourself. There is a callback form,
+`record.forEachMismatch(cb, opts?)`, which allocates nothing per difference and
+takes a reference window to report within.
+
+Substitutions need either an `MD` tag on the read or the reference bases, and
+most aligners leave `MD` off. `fetchReferenceSequence` is how you supply them:
+
+```typescript
+const bam = new BamFile({
+  bamPath: 'test.bam',
+  fetchReferenceSequence: async (refName, start, end) =>
+    myGenome.getSequence(refName, start, end),
+})
+
+// one sequence fetch for the whole query, and only if some read needs it
+const records = await bam.getRecordsForRange('ctgA', 0, 50000)
+records[0].getMismatches()
+// [{ code: 88 /* 'X' */, refPos: 188, length: 1, bases: 'A', qual: 17,
+//    refBaseCode: 84 /* 'T' */, clipLength: 0 }, ...]
+```
+
+Without it, a read lacking `MD` still reports its indels and clips, but no
+substitutions — nothing in the record says where they are. See
+[docs/api.md](docs/api.md#mismatches) for the field meanings and for reads
+longer than the region you are looking at.
+
 ## Decompressing on a worker pool
 
 BGZF decompression is 70-90% of a cold query, and BGZF blocks are independently

package/dist/bamFile.d.ts

@@ -3,6 +3,7 @@ import BAI from './bai.ts';
 import CSI from './csi.ts';
 import BAMFeature from './record.ts';
 import type Chunk from './chunk.ts';
+import type { PackedReference } from './reference.ts';
 import type { BamOpts, BaseOpts } from './util.ts';
 import type { BgzfWorkerPool } from '@gmod/bgzf-filehandle';
 import type { SharedBudget } from '@gmod/shared-read-cache';
@@ -17,7 +18,35 @@ export interface BamRecordLike {
     next_refid: number;
     flags: number;
     tags: Record<string, unknown>;
+    /**
+     * Optional, and read only to decide whether a read needs reference bases at
+     * all — a read with an MD tag carries its own. A `recordClass` without it is
+     * treated as having no MD, i.e. as always wanting the reference.
+     */
+    NUMERIC_MD?: Uint8Array | undefined;
+    /**
+     * Optional; see {@link BamRecord.setReference}. A `recordClass` that does not
+     * implement it simply never gets a reference bound, whatever
+     * `fetchReferenceSequence` returns.
+     */
+    setReference?: (ref: PackedReference) => void;
 }
+/**
+ * Supplies reference bases for a region, so reads with no MD tag can still
+ * report their substitutions. See {@link BamFile}'s option of the same name.
+ *
+ * `refName` is the name the query used, unchanged — `renameRefSeqs` maps the
+ * FILE's names into the caller's namespace, and this callback is on the
+ * caller's side of that. `start`/`end` are 0-based half-open.
+ *
+ * **The bases returned must begin at `start`.** Returning fewer than asked for
+ * is fine and is taken as `[start, start + seq.length)` — the end of a contig,
+ * or a source declining to hand over a huge span — and reads the shorter region
+ * does not cover are then left unresolved. Returning bases from somewhere else,
+ * e.g. clipping the LEFT of the requested range, cannot be detected and
+ * resolves every read against the wrong position.
+ */
+export type ReferenceSequenceFetcher = (refName: string, start: number, end: number, opts?: BaseOpts) => Promise<string>;
 export type BamRecordClass<T extends BamRecordLike = BAMFeature> = new (byteArray: Uint8Array, start: number, end: number, fileOffset: number, dataView: DataView) => T;
 export declare const BAM_MAGIC = 21840194;
 interface ChunkEntry<T> {
@@ -46,7 +75,9 @@ export default class BamFile<T extends BamRecordLike = BAMFeature> {
     private RecordClass;
     /** see the constructor option of the same name */
     private bgzfWorkerPool?;
-    constructor({ bamFilehandle, bamPath, bamUrl, baiPath, baiFilehandle, baiUrl, csiPath, csiFilehandle, csiUrl, htsget, renameRefSeqs, recordClass, maxCacheBytes, cacheIdleTimeoutMs, cacheBudget, bgzfWorkerPool, }: {
+    /** see the constructor option of the same name */
+    fetchReferenceSequence?: ReferenceSequenceFetcher;
+    constructor({ bamFilehandle, bamPath, bamUrl, baiPath, baiFilehandle, baiUrl, csiPath, csiFilehandle, csiUrl, htsget, renameRefSeqs, recordClass, maxCacheBytes, cacheIdleTimeoutMs, cacheBudget, bgzfWorkerPool, fetchReferenceSequence, }: {
         bamFilehandle?: GenericFilehandle;
         bamPath?: string;
         bamUrl?: string;
@@ -135,6 +166,33 @@ export default class BamFile<T extends BamRecordLike = BAMFeature> {
          * in-process path, so this is safe to pass unconditionally.
          */
         bgzfWorkerPool?: BgzfWorkerPool | Promise<BgzfWorkerPool | undefined> | undefined;
+        /**
+         * Reference bases for a region, as `(refName, start, end, opts) =>
+         * Promise<string>`. Only reads that carry no `MD` tag need it, and it is
+         * only what {@link BamRecord.forEachMismatch} uses — nothing else in a
+         * query touches the reference.
+         *
+         * Without it, a read lacking MD still reports its indels and clips but no
+         * substitutions at all: neither the CIGAR nor SEQ says where they are.
+         * That is most aligners' output — minimap2 and bwa both leave MD off unless
+         * asked — so this is the difference between mismatches rendering and not.
+         *
+         * `getRecordsForRange` calls it at most ONCE per query, for the span of the
+         * reads that need it, and binds the result to each of them (see
+         * {@link BamRecord.setReference}). A query whose reads all carry MD does
+         * not call it at all.
+         *
+         * **The span asked for is the reads' union, not the query's**: the query's
+         * range plus however far its edge reads overhang it. Usually that is a few
+         * hundred bases more for Illumina and a couple of Mb for ultra-long ONT,
+         * but a BAM holding whole chromosomes as reads can make it a chromosome.
+         * Nothing here clamps that for you, because only you know what your
+         * sequence source can afford — clamp inside the callback and return the
+         * shorter region; reads it does not cover are then simply left unresolved,
+         * and {@link BamRecord.forEachMismatch}'s `opts.ref` is the windowed way to
+         * handle one of those reads.
+         */
+        fetchReferenceSequence?: ReferenceSequenceFetcher;
     });
     getHeaderPre(opts?: BaseOpts): Promise<{
         tag: string;
@@ -201,6 +259,41 @@ export default class BamFile<T extends BamRecordLike = BAMFeature> {
      * it for every other query still holding that read. See ADR 0006.
      */
     getRecordsForRange(chr: string, min: number, max: number, opts?: BamOpts): Promise<T[]>;
+    /**
+     * Reference bases for a region, packed for
+     * {@link BamRecord.forEachMismatch}'s `opts.ref`, or undefined when no
+     * `fetchReferenceSequence` was configured.
+     *
+     * The way to resolve a read that is longer than the region you are looking at
+     * — a contig or a whole chromosome stored as one BAM read. Those are never
+     * bound to a record automatically, since binding a partial region to a
+     * record shared between queries is the hazard ADR 0006 is about; walking one
+     * with a window and a region of your own choosing has no such problem:
+     *
+     * ```js
+     * const ref = await bam.getReferenceRegion('chr1', start, end)
+     * record.forEachMismatch(cb, { ref, start, end })
+     * ```
+     */
+    getReferenceRegion(refName: string, start: number, end: number, opts?: BaseOpts): Promise<PackedReference | undefined>;
+    /**
+     * Fetch reference bases for the reads in `records` that have no MD tag, and
+     * bind them to those reads so their substitutions resolve. A no-op unless
+     * `fetchReferenceSequence` was configured, and it issues at most one fetch.
+     *
+     * The span fetched is the union of the reads that need it, NOT the queried
+     * range: a read overhanging the range is only bound to a region covering all
+     * of it, because the records are shared between queries and a binding that
+     * varied by query would make one query's reads answer out of another's region
+     * (ADR 0006, ADR 0020). Reads on another reference — `viewAsPairs` mates with
+     * `pairAcrossChr` — are left out for the same reason, and unbound.
+     *
+     * Nothing clamps that union, since only the callback knows what its sequence
+     * source can afford; a callback that returns a shorter region than it was
+     * asked for leaves the reads it does not cover unbound, which is the same
+     * outcome by a route the consumer controls.
+     */
+    protected _applyReferenceSequence(records: T[], chrId: number, refName: string, opts?: BaseOpts): Promise<void>;
     private _cachedChunkFeatures;
     private _fetchChunkFeatures;
     fetchPairs(chrId: number, records: T[], opts: BamOpts): Promise<T[]>;

package/dist/bamFile.js

@@ -12,6 +12,7 @@ const bai_ts_1 = __importDefault(require("./bai.js"));
 const csi_ts_1 = __importDefault(require("./csi.js"));
 const nullFilehandle_ts_1 = __importDefault(require("./nullFilehandle.js"));
 const record_ts_1 = __importDefault(require("./record.js"));
+const reference_ts_1 = require("./reference.js");
 const sam_ts_1 = require("./sam.js");
 const util_ts_1 = require("./util.js");
 exports.BAM_MAGIC = 21840194;
@@ -112,9 +113,12 @@ class BamFile {
     RecordClass;
     /** see the constructor option of the same name */
     bgzfWorkerPool;
-    constructor({ bamFilehandle, bamPath, bamUrl, baiPath, baiFilehandle, baiUrl, csiPath, csiFilehandle, csiUrl, htsget, renameRefSeqs = n => n, recordClass, maxCacheBytes = exports.DEFAULT_MAX_CACHE_BYTES, cacheIdleTimeoutMs = exports.DEFAULT_CACHE_IDLE_TIMEOUT_MS, cacheBudget, bgzfWorkerPool, }) {
+    /** see the constructor option of the same name */
+    fetchReferenceSequence;
+    constructor({ bamFilehandle, bamPath, bamUrl, baiPath, baiFilehandle, baiUrl, csiPath, csiFilehandle, csiUrl, htsget, renameRefSeqs = n => n, recordClass, maxCacheBytes = exports.DEFAULT_MAX_CACHE_BYTES, cacheIdleTimeoutMs = exports.DEFAULT_CACHE_IDLE_TIMEOUT_MS, cacheBudget, bgzfWorkerPool, fetchReferenceSequence, }) {
         this.renameRefSeq = renameRefSeqs;
         this.bgzfWorkerPool = bgzfWorkerPool;
+        this.fetchReferenceSequence = fetchReferenceSequence;
         this.RecordClass = (recordClass ?? record_ts_1.default);
         this.chunkFeatureCache = new shared_read_cache_1.SharedReadCache({
             maxSize: maxCacheBytes,
@@ -269,7 +273,90 @@ class BamFile {
             return [];
         }
         const chunks = await this.index.blocksForRange(chrId, min - 1, max, opts);
-        return this._fetchChunkFeatures(chunks, chrId, min, max, opts);
+        return this._fetchChunkFeatures(chunks, chrId, chr, min, max, opts);
+    }
+    /**
+     * Reference bases for a region, packed for
+     * {@link BamRecord.forEachMismatch}'s `opts.ref`, or undefined when no
+     * `fetchReferenceSequence` was configured.
+     *
+     * The way to resolve a read that is longer than the region you are looking at
+     * — a contig or a whole chromosome stored as one BAM read. Those are never
+     * bound to a record automatically, since binding a partial region to a
+     * record shared between queries is the hazard ADR 0006 is about; walking one
+     * with a window and a region of your own choosing has no such problem:
+     *
+     * ```js
+     * const ref = await bam.getReferenceRegion('chr1', start, end)
+     * record.forEachMismatch(cb, { ref, start, end })
+     * ```
+     */
+    async getReferenceRegion(refName, start, end, opts) {
+        const fetchReferenceSequence = this.fetchReferenceSequence;
+        if (!fetchReferenceSequence) {
+            return undefined;
+        }
+        // Packed once for the region rather than per read — the walk compares two
+        // bases per byte against the read's own packed SEQ, and this is the only
+        // per-base pass in it. Length comes from what came back rather than from
+        // what was asked for, so a callback that clips at the end of the contig
+        // still leaves the bases it did return usable.
+        return (0, reference_ts_1.packReference)(await fetchReferenceSequence(refName, start, end, opts), start);
+    }
+    /**
+     * Fetch reference bases for the reads in `records` that have no MD tag, and
+     * bind them to those reads so their substitutions resolve. A no-op unless
+     * `fetchReferenceSequence` was configured, and it issues at most one fetch.
+     *
+     * The span fetched is the union of the reads that need it, NOT the queried
+     * range: a read overhanging the range is only bound to a region covering all
+     * of it, because the records are shared between queries and a binding that
+     * varied by query would make one query's reads answer out of another's region
+     * (ADR 0006, ADR 0020). Reads on another reference — `viewAsPairs` mates with
+     * `pairAcrossChr` — are left out for the same reason, and unbound.
+     *
+     * Nothing clamps that union, since only the callback knows what its sequence
+     * source can afford; a callback that returns a shorter region than it was
+     * asked for leaves the reads it does not cover unbound, which is the same
+     * outcome by a route the consumer controls.
+     */
+    async _applyReferenceSequence(records, chrId, refName, opts = {}) {
+        const fetchReferenceSequence = this.fetchReferenceSequence;
+        if (!fetchReferenceSequence) {
+            return;
+        }
+        let start = Infinity;
+        let end = 0;
+        for (let i = 0, l = records.length; i < l; i++) {
+            const record = records[i];
+            if (record.ref_id === chrId &&
+                !record.NUMERIC_MD &&
+                record.setReference) {
+                if (record.start < start) {
+                    start = record.start;
+                }
+                if (record.end > end) {
+                    end = record.end;
+                }
+            }
+        }
+        // every read carries MD, or there are no reads: nothing to fetch
+        if (start >= end) {
+            return;
+        }
+        const ref = await this.getReferenceRegion(refName, start, end, opts);
+        if (!ref) {
+            return;
+        }
+        for (let i = 0, l = records.length; i < l; i++) {
+            const record = records[i];
+            if (record.ref_id === chrId &&
+                !record.NUMERIC_MD &&
+                record.setReference &&
+                (0, reference_ts_1.referenceCovers)(ref, record.start, record.end)) {
+                record.setReference(ref);
+            }
+        }
     }
     // Parsed records for a chunk, reading and decompressing it only on a miss.
     // Every path that wants a chunk's features goes through here — mate lookups
@@ -288,7 +375,7 @@ class BamFile {
         const entry = await this.chunkFeatureCache.get(chunk, opts.signal);
         return entry.features;
     }
-    async _fetchChunkFeatures(chunks, chrId, min, max, opts = {}) {
+    async _fetchChunkFeatures(chunks, chrId, chr, min, max, opts = {}) {
         const { viewAsPairs, onProgress } = opts;
         const result = [];
         let totalBytes = 0;
@@ -375,6 +462,10 @@ class BamFile {
                 result.push(pairs[i]);
             }
         }
+        // After the pairs, so a mate fetched from another chunk is resolved on the
+        // same terms as the reads it was fetched for. A no-op without
+        // `fetchReferenceSequence`, which is the default.
+        await this._applyReferenceSequence(result, chrId, chr, opts);
         return result;
     }
     async fetchPairs(chrId, records, opts) {

package/dist/bamFile.js.map

@@ -1 +1 @@
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package/dist/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/dist/htsget.js

@@ -113,6 +113,7 @@ class HtsgetFile extends bamFile_ts_1.default {
             recordClass: args.recordClass,
             maxCacheBytes: args.maxCacheBytes,
             cacheIdleTimeoutMs: args.cacheIdleTimeoutMs,
+            fetchReferenceSequence: args.fetchReferenceSequence,
         });
         this.baseUrl = args.baseUrl;
         this.trackId = args.trackId;
@@ -139,7 +140,9 @@ class HtsgetFile extends bamFile_ts_1.default {
         const uncba = await this.fetchTicket(`referenceName=${chr}&start=${min}&end=${max}&format=BAM`, opts);
         const zero = new virtualOffset_ts_1.VirtualOffset(0, 0);
         const records = this.readBamFeatures(uncba.subarray(recordsOffset(uncba)), [], [], new chunk_ts_1.default(zero, zero, 0));
-        return (0, util_ts_1.appendInRange)(records, chrId, min, max);
+        const result = (0, util_ts_1.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/dist/htsget.js.map

@@ -1 +1 @@
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+{"version":3,"file":"htsget.js","sourceRoot":"","sources":["../src/htsget.ts"],"names":[],"mappings":";;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;;AAAA,2DAA6C;AAE7C,2DAAiD;AACjD,0DAA8B;AAC9B,uCAAyE;AACzE,yDAAkD;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,sBAAS,EAAE,CAAC;QACrE,OAAO,CAAC,CAAA;IACV,CAAC;IACD,MAAM,IAAI,GAAG,IAAA,sBAAY,EAAC,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,IAAA,0BAAgB,EACrB,MAAM,OAAO,CAAC,GAAG,CACf,GAAG,CAAC,GAAG,CAAC,KAAK,EAAC,CAAC,EAAC,EAAE,CAAC,IAAA,uBAAK,EAAC,MAAM,UAAU,CAAC,OAAO,EAAE,CAAC,EAAE,IAAI,CAAC,CAAC,CAAC,CAC9D,CACF,CAAA;AACH,CAAC;AAED,MAAqB,UAEnB,SAAQ,oBAAU;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,gCAAa,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,kBAAK,CAAC,IAAI,EAAE,IAAI,EAAE,CAAC,CAAC,CACzB,CAAA;QACD,MAAM,MAAM,GAAG,IAAA,uBAAa,EAAC,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;AAzGD,6BAyGC"}

package/dist/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/dist/index.js

@@ -3,7 +3,7 @@ var __importDefault = (this && this.__importDefault) || function (mod) {
     return (mod && mod.__esModule) ? mod : { "default": mod };
 };
 Object.defineProperty(exports, "__esModule", { value: true });
-exports.HtsgetFile = exports.BamRecord = exports.CSI = exports.BamFile = exports.DEFAULT_MAX_CACHE_BYTES = exports.DEFAULT_CACHE_IDLE_TIMEOUT_MS = exports.BAI = void 0;
+exports.packReference = exports.forEachMismatchNumeric = exports.MISMATCH_SUBST = exports.MISMATCH_SOFT_CLIP = exports.MISMATCH_REF_SKIP = exports.MISMATCH_INSERTION = exports.MISMATCH_HARD_CLIP = exports.MISMATCH_DELETION = exports.HtsgetFile = exports.BamRecord = exports.CSI = exports.BamFile = exports.DEFAULT_MAX_CACHE_BYTES = exports.DEFAULT_CACHE_IDLE_TIMEOUT_MS = exports.BAI = void 0;
 var bai_ts_1 = require("./bai.js");
 Object.defineProperty(exports, "BAI", { enumerable: true, get: function () { return __importDefault(bai_ts_1).default; } });
 var bamFile_ts_1 = require("./bamFile.js");
@@ -16,4 +16,18 @@ var record_ts_1 = require("./record.js");
 Object.defineProperty(exports, "BamRecord", { enumerable: true, get: function () { return __importDefault(record_ts_1).default; } });
 var htsget_ts_1 = require("./htsget.js");
 Object.defineProperty(exports, "HtsgetFile", { enumerable: true, get: function () { return __importDefault(htsget_ts_1).default; } });
+// 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.
+var mismatches_ts_1 = require("./mismatches.js");
+Object.defineProperty(exports, "MISMATCH_DELETION", { enumerable: true, get: function () { return mismatches_ts_1.MISMATCH_DELETION; } });
+Object.defineProperty(exports, "MISMATCH_HARD_CLIP", { enumerable: true, get: function () { return mismatches_ts_1.MISMATCH_HARD_CLIP; } });
+Object.defineProperty(exports, "MISMATCH_INSERTION", { enumerable: true, get: function () { return mismatches_ts_1.MISMATCH_INSERTION; } });
+Object.defineProperty(exports, "MISMATCH_REF_SKIP", { enumerable: true, get: function () { return mismatches_ts_1.MISMATCH_REF_SKIP; } });
+Object.defineProperty(exports, "MISMATCH_SOFT_CLIP", { enumerable: true, get: function () { return mismatches_ts_1.MISMATCH_SOFT_CLIP; } });
+Object.defineProperty(exports, "MISMATCH_SUBST", { enumerable: true, get: function () { return mismatches_ts_1.MISMATCH_SUBST; } });
+Object.defineProperty(exports, "forEachMismatchNumeric", { enumerable: true, get: function () { return mismatches_ts_1.forEachMismatchNumeric; } });
+var reference_ts_1 = require("./reference.js");
+Object.defineProperty(exports, "packReference", { enumerable: true, get: function () { return reference_ts_1.packReference; } });
 //# sourceMappingURL=index.js.map

package/dist/index.js.map

@@ -1 +1 @@
-{"version":3,"file":"index.js","sourceRoot":"","sources":["../src/index.ts"],"names":[],"mappings":";;;;;;AAAA,mCAAyC;AAAhC,8GAAA,OAAO,OAAO;AACvB,2CAIqB;AAHnB,2HAAA,6BAA6B,OAAA;AAC7B,qHAAA,uBAAuB,OAAA;AACvB,sHAAA,OAAO,OAAW;AAEpB,mCAAyC;AAAhC,8GAAA,OAAO,OAAO;AACvB,yCAAkD;AAAzC,uHAAA,OAAO,OAAa;AAC7B,yCAAmD;AAA1C,wHAAA,OAAO,OAAc"}
+{"version":3,"file":"index.js","sourceRoot":"","sources":["../src/index.ts"],"names":[],"mappings":";;;;;;AAAA,mCAAyC;AAAhC,8GAAA,OAAO,OAAO;AACvB,2CAIqB;AAHnB,2HAAA,6BAA6B,OAAA;AAC7B,qHAAA,uBAAuB,OAAA;AACvB,sHAAA,OAAO,OAAW;AAEpB,mCAAyC;AAAhC,8GAAA,OAAO,OAAO;AACvB,yCAAkD;AAAzC,uHAAA,OAAO,OAAa;AAC7B,yCAAmD;AAA1C,wHAAA,OAAO,OAAc;AAE9B,0EAA0E;AAC1E,+EAA+E;AAC/E,2EAA2E;AAC3E,2BAA2B;AAC3B,iDAQwB;AAPtB,kHAAA,iBAAiB,OAAA;AACjB,mHAAA,kBAAkB,OAAA;AAClB,mHAAA,kBAAkB,OAAA;AAClB,kHAAA,iBAAiB,OAAA;AACjB,mHAAA,kBAAkB,OAAA;AAClB,+GAAA,cAAc,OAAA;AACd,uHAAA,sBAAsB,OAAA;AAExB,+CAA8C;AAArC,6GAAA,aAAa,OAAA"}

package/dist/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;