@gmod/bam 7.3.4 → 7.4.0

package/esm/bamFile.js

@@ -1,5 +1,4 @@
 import { unzip, unzipChunkSlice } from '@gmod/bgzf-filehandle';
-import QuickLRU from '@jbrowse/quick-lru';
 import crc32 from 'crc/calculators/crc32';
 import { LocalFile, RemoteFile } from 'generic-filehandle2';
 import BAI from "./bai.js";
@@ -7,16 +6,75 @@ import CSI from "./csi.js";
 import NullFilehandle from "./nullFilehandle.js";
 import BAMFeature from "./record.js";
 import { parseHeaderText } from "./sam.js";
-import { appendInRange, applyFilters, filterCacheKey, parseRefSeqs, } from "./util.js";
+import { appendInRange, applyFilters, parseRefSeqs } from "./util.js";
 export const BAM_MAGIC = 21840194;
 const blockLen = 1 << 16;
 function resolveFilehandle(filehandle, path, url) {
     return (filehandle ??
         (path ? new LocalFile(path) : url ? new RemoteFile(url) : undefined));
 }
-function chunkCacheKey(chunk, filterBy) {
+// Keyed on the chunk's byte span only, not on filterBy: the cached value is the
+// unfiltered parsed records (decompression + parse is the expensive part).
+// Filters are applied cheaply on retrieval so toggling a filter over the same
+// region is a cache hit rather than a re-decompress.
+function chunkCacheKey(chunk) {
     const { minv, maxv } = chunk;
-    return `${minv.blockPosition}:${minv.dataPosition}-${maxv.blockPosition}:${maxv.dataPosition}${filterCacheKey(filterBy)}`;
+    return `${minv.blockPosition}:${minv.dataPosition}-${maxv.blockPosition}:${maxv.dataPosition}`;
+}
+// Every record in an entry is a view into its chunk's decompressed buffer, so
+// caching one entry pins that whole buffer — 8MB apiece on the nanopore and
+// 2kb-read test files, and optimizeChunks merges spans up to 5MB *compressed*,
+// so tens of MB is possible. A count-based LRU therefore gives no bound on
+// memory at all, which is why this budgets by decompressed bytes instead.
+export const DEFAULT_MAX_CACHE_BYTES = 100 * 1024 * 1024;
+class ChunkFeatureCache {
+    maxBytes;
+    entries = new Map();
+    bytes = 0;
+    constructor(maxBytes) {
+        this.maxBytes = maxBytes;
+    }
+    get size() {
+        return this.entries.size;
+    }
+    get byteSize() {
+        return this.bytes;
+    }
+    get(key) {
+        const entry = this.entries.get(key);
+        if (entry) {
+            // re-insert so Map iteration order stays least-recently-used first
+            this.entries.delete(key);
+            this.entries.set(key, entry);
+        }
+        return entry;
+    }
+    set(key, entry) {
+        this.delete(key);
+        this.entries.set(key, entry);
+        this.bytes += entry.bytes;
+        // Evict from the least-recently-used end. The size > 1 guard means a single
+        // chunk larger than the whole budget is still kept: the caller needs it for
+        // the query in flight, and dropping it would only force a re-decompress.
+        const lru = this.entries.keys();
+        while (this.bytes > this.maxBytes && this.entries.size > 1) {
+            this.delete(lru.next().value);
+        }
+    }
+    delete(key) {
+        const entry = this.entries.get(key);
+        if (entry) {
+            this.entries.delete(key);
+            this.bytes -= entry.bytes;
+        }
+    }
+    clear() {
+        this.entries.clear();
+        this.bytes = 0;
+    }
+    [Symbol.iterator]() {
+        return this.entries[Symbol.iterator]();
+    }
 }
 export default class BamFile {
     renameRefSeq;
@@ -29,13 +87,12 @@ export default class BamFile {
     headerP;
     // Cache for parsed features by chunk
     // When a new chunk overlaps a cached chunk, we evict the cached one
-    chunkFeatureCache = new QuickLRU({
-        maxSize: 100,
-    });
+    chunkFeatureCache;
     RecordClass;
-    constructor({ bamFilehandle, bamPath, bamUrl, baiPath, baiFilehandle, baiUrl, csiPath, csiFilehandle, csiUrl, htsget, renameRefSeqs = n => n, recordClass, }) {
+    constructor({ bamFilehandle, bamPath, bamUrl, baiPath, baiFilehandle, baiUrl, csiPath, csiFilehandle, csiUrl, htsget, renameRefSeqs = n => n, recordClass, maxCacheBytes = DEFAULT_MAX_CACHE_BYTES, }) {
         this.renameRefSeq = renameRefSeqs;
         this.RecordClass = (recordClass ?? BAMFeature);
+        this.chunkFeatureCache = new ChunkFeatureCache(maxCacheBytes);
         const bamFh = resolveFilehandle(bamFilehandle, bamPath, bamUrl);
         if (bamFh) {
             this.bam = bamFh;
@@ -75,7 +132,7 @@ export default class BamFile {
             ? await this.bam.readFile()
             : await this.bam.read(readLen, 0);
         let uncba = await unzip(buffer);
-        const dataView = new DataView(uncba.buffer);
+        const dataView = new DataView(uncba.buffer, uncba.byteOffset, uncba.byteLength);
         if (dataView.getInt32(0, true) !== BAM_MAGIC) {
             throw new Error('Not a BAM file');
         }
@@ -123,7 +180,7 @@ export default class BamFile {
             return [];
         }
         const chunks = await this.index.blocksForRange(chrId, min - 1, max, opts);
-        return this._fetchChunkFeaturesDirect(chunks, chrId, min, max, opts);
+        return this._fetchChunkFeatures(chunks, chrId, min, max, opts);
     }
     // Evict any cached chunks whose block range overlaps [minBlock, maxBlock]
     evictOverlappingChunks(minBlock, maxBlock) {
@@ -133,7 +190,7 @@ export default class BamFile {
             }
         }
     }
-    async _fetchChunkFeaturesDirect(chunks, chrId, min, max, opts = {}) {
+    async _fetchChunkFeatures(chunks, chrId, min, max, opts = {}) {
         const { viewAsPairs, filterBy, onProgress } = opts;
         const result = [];
         let totalBytes = 0;
@@ -144,24 +201,19 @@ export default class BamFile {
         onProgress?.(0, totalBytes);
         for (let ci = 0, cl = chunks.length; ci < cl; ci++) {
             const chunk = chunks[ci];
-            const cacheKey = chunkCacheKey(chunk, filterBy);
+            const cacheKey = chunkCacheKey(chunk);
             const minBlock = chunk.minv.blockPosition;
             const maxBlock = chunk.maxv.blockPosition;
-            let records;
-            const cached = this.chunkFeatureCache.get(cacheKey);
-            if (cached) {
-                records = cached.features;
-            }
-            else {
+            let cached = this.chunkFeatureCache.get(cacheKey);
+            if (!cached) {
                 this.evictOverlappingChunks(minBlock, maxBlock);
-                const allRecords = await this._readChunkFeatures(chunk, opts);
-                records = filterBy ? applyFilters(allRecords, filterBy) : allRecords;
-                this.chunkFeatureCache.set(cacheKey, {
-                    minBlock,
-                    maxBlock,
-                    features: records,
-                });
+                const { features, bytes } = await this._readChunkFeatures(chunk, opts);
+                cached = { minBlock, maxBlock, bytes, features };
+                this.chunkFeatureCache.set(cacheKey, cached);
             }
+            const records = filterBy
+                ? applyFilters(cached.features, filterBy)
+                : cached.features;
             downloadedBytes += chunk.fetchedSize();
             onProgress?.(downloadedBytes, totalBytes);
             appendInRange(records, chrId, min, max, result);
@@ -176,12 +228,15 @@ export default class BamFile {
     }
     async fetchPairs(chrId, records, opts) {
         const { pairAcrossChr, maxInsertSize = 200000 } = opts;
-        const readNameCounts = {};
+        // Map, not a plain object: read names come from the file, and on a plain
+        // object a read named "constructor" would read back Object.prototype's and
+        // make the count NaN.
+        const readNameCounts = new Map();
         const readIds = new Set();
         for (let i = 0, l = records.length; i < l; i++) {
             const r = records[i];
             const name = r.name;
-            readNameCounts[name] = (readNameCounts[name] ?? 0) + 1;
+            readNameCounts.set(name, (readNameCounts.get(name) ?? 0) + 1);
             readIds.add(r.fileOffset);
         }
         const matePromises = [];
@@ -189,7 +244,7 @@ export default class BamFile {
             const f = records[i];
             const name = f.name;
             if (this.index &&
-                readNameCounts[name] === 1 &&
+                readNameCounts.get(name) === 1 &&
                 (pairAcrossChr ||
                     (f.next_refid === chrId &&
                         Math.abs(f.start - f.next_pos) < maxInsertSize))) {
@@ -206,11 +261,11 @@ export default class BamFile {
             }
         }
         const mateFeatLists = await Promise.all([...map.values()].map(async (c) => {
-            const features = await this._readChunkFeatures(c, opts);
+            const { features } = await this._readChunkFeatures(c, opts);
             const mateRecs = [];
             for (let i = 0, l = features.length; i < l; i++) {
                 const feature = features[i];
-                if (readNameCounts[feature.name] === 1 &&
+                if (readNameCounts.get(feature.name) === 1 &&
                     !readIds.has(feature.fileOffset)) {
                     mateRecs.push(feature);
                 }
@@ -229,13 +284,16 @@ export default class BamFile {
             signal: opts.signal,
         });
         const { buffer: data, cpositions, dpositions, } = await unzipChunkSlice(buf, chunk);
-        return this.readBamFeatures(data, cpositions, dpositions, chunk);
+        return {
+            features: this.readBamFeatures(data, cpositions, dpositions, chunk),
+            bytes: data.byteLength,
+        };
     }
-    async readBamFeatures(ba, cpositions, dpositions, chunk) {
+    readBamFeatures(ba, cpositions, dpositions, chunk) {
         let blockStart = 0;
         const sink = [];
         let pos = 0;
-        const dataView = new DataView(ba.buffer);
+        const dataView = new DataView(ba.buffer, ba.byteOffset, ba.byteLength);
         const hasDpositions = dpositions.length > 0;
         const hasCpositions = cpositions.length > 0;
         while (blockStart + 4 < ba.length) {

package/esm/bamFile.js.map

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package/esm/csi.js

@@ -22,7 +22,7 @@ export default class CSI extends IndexFile {
         return [];
     }
     parseAuxData(bytes, offset) {
-        const dataView = new DataView(bytes.buffer);
+        const dataView = new DataView(bytes.buffer, bytes.byteOffset, bytes.byteLength);
         const formatFlags = dataView.getUint32(offset, true);
         const coordinateType = formatFlags & 0x10000 ? 'zero-based-half-open' : '1-based-closed';
         const format = ['generic', 'SAM', 'VCF'][formatFlags & 0xf];
@@ -53,7 +53,7 @@ export default class CSI extends IndexFile {
     async _parse(opts) {
         const buffer = await this.filehandle.readFile(opts);
         const bytes = await unzip(buffer);
-        const dataView = new DataView(bytes.buffer);
+        const dataView = new DataView(bytes.buffer, bytes.byteOffset, bytes.byteLength);
         let csiVersion;
         const magic = dataView.getUint32(0, true);
         if (magic === CSI1_MAGIC) {

package/esm/csi.js.map

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

@@ -47,7 +47,7 @@ export default class HtsgetFile extends BamFile {
             signal: opts?.signal,
         });
         const zero = new VirtualOffset(0, 0);
-        const allRecords = await this.readBamFeatures(uncba, [], [], new Chunk(zero, zero, 0));
+        const allRecords = this.readBamFeatures(uncba, [], [], new Chunk(zero, zero, 0));
         return appendInRange(allRecords, chrId, min, max);
     }
     async getHeaderPre(opts = {}) {
@@ -57,7 +57,7 @@ export default class HtsgetFile extends BamFile {
         const uncba = await fetchAndConcat(data.htsget.urls, {
             signal: opts.signal,
         });
-        const dataView = new DataView(uncba.buffer);
+        const dataView = new DataView(uncba.buffer, uncba.byteOffset, uncba.byteLength);
         if (dataView.getInt32(0, true) !== BAM_MAGIC) {
             throw new Error('Not a BAM file');
         }

package/esm/htsget.js.map

@@ -1 +1 @@
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package/esm/index.d.ts

@@ -1,5 +1,5 @@
 export { default as BAI } from './bai.ts';
-export { default as BamFile } from './bamFile.ts';
+export { DEFAULT_MAX_CACHE_BYTES, default as BamFile } from './bamFile.ts';
 export { default as CSI } from './csi.ts';
 export { default as BamRecord } from './record.ts';
 export { default as HtsgetFile } from './htsget.ts';

package/esm/index.js

@@ -1,5 +1,5 @@
 export { default as BAI } from "./bai.js";
-export { default as BamFile } from "./bamFile.js";
+export { DEFAULT_MAX_CACHE_BYTES, default as BamFile } from "./bamFile.js";
 export { default as CSI } from "./csi.js";
 export { default as BamRecord } from "./record.js";
 export { default as HtsgetFile } from "./htsget.js";

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,EAAE,OAAO,IAAI,OAAO,EAAE,MAAM,cAAc,CAAA;AACjD,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,EAAE,uBAAuB,EAAE,OAAO,IAAI,OAAO,EAAE,MAAM,cAAc,CAAA;AAC1E,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"}

package/esm/record.d.ts

@@ -1,3 +1,4 @@
+export type NumericCigar = Uint32Array | Int32Array | number[];
 export interface Bytes {
     start: number;
     end: number;
@@ -55,7 +56,7 @@ export default class BamRecord {
     private _computeLengthOnRef;
     private _computeNumericCigar;
     get length_on_ref(): number;
-    get NUMERIC_CIGAR(): number[] | Uint32Array<ArrayBufferLike>;
+    get NUMERIC_CIGAR(): NumericCigar;
     get CIGAR(): string;
     get num_cigar_ops(): number;
     get num_cigar_bytes(): number;

package/esm/record.js

@@ -1,14 +1,41 @@
 import { CIGAR_REF_SKIP, CIGAR_SOFT_CLIP } from "./cigar.js";
 import Constants from "./constants.js";
-const SEQRET_DECODER = '=ACMGRSVTWYHKDBN'.split('');
-// precomputed pair orientation strings indexed by ((flags >> 4) & 0xF) | (isize > 0 ? 16 : 0)
-// bits 0-3 encode flag bits 0x10(reverse),0x20(mate reverse),0x40(read1),0x80(read2)
-// bit 4 encodes whether isize > 0
+const SEQRET = '=ACMGRSVTWYHKDBN';
+const SEQRET_DECODER = SEQRET.split('');
+const SEQRET_CODES = Uint8Array.from(SEQRET, c => c.charCodeAt(0));
+// Both bases of a SEQ byte, precomputed for all 256 bytes so decoding advances a
+// byte at a time. Two forms because `seq` has two strategies (see below): packed
+// ASCII codes for a single Uint16Array store, and the 2-char string to append.
+// Byte order within the u16 depends on host endianness.
+const LITTLE_ENDIAN = new Uint16Array(Uint8Array.of(1, 0).buffer)[0] === 1;
+const SEQRET_PAIR_CODES = new Uint16Array(256);
+const SEQRET_PAIR_STRINGS = new Array(256);
+for (let hi = 0; hi < 16; hi++) {
+    for (let lo = 0; lo < 16; lo++) {
+        const h = SEQRET_CODES[hi];
+        const l = SEQRET_CODES[lo];
+        SEQRET_PAIR_CODES[(hi << 4) | lo] = LITTLE_ENDIAN
+            ? h | (l << 8)
+            : (h << 8) | l;
+        SEQRET_PAIR_STRINGS[(hi << 4) | lo] =
+            SEQRET_DECODER[hi] + SEQRET_DECODER[lo];
+    }
+}
+// Read length at which building a byte buffer and calling TextDecoder once
+// overtakes plain string concatenation. Below it concat wins by 2-4x (rope
+// building is cheap and the decode has fixed overhead); above it the decoder
+// wins by 5-8x. Measured crossover is ~300bp, i.e. just past typical Illumina
+// read lengths.
+const SEQ_DECODER_THRESHOLD = 300;
+// Precomputed pair orientation strings, indexed by
+//   ((flags >> 4) & 0x7) | (selfIsLeft ? 8 : 0)
+// bits 0-2 are flag bits 0x10 (self reverse), 0x20 (mate reverse), 0x40 (read1);
+// bit 3 is whether this read is the leftmost of the pair. The read2 flag (0x80)
+// is deliberately not consulted — "not read1" is what decides the numbering, so
+// a record with neither flag set reads the same as read2.
 // prettier-ignore
 const PAIR_ORIENTATION_TABLE = [
-    'F F ', 'F R ', 'R F ', 'R R ', 'F2F1', 'F2R1', 'R2F1', 'R2R1',
     'F1F2', 'F1R2', 'R1F2', 'R1R2', 'F2F1', 'F2R1', 'R2F1', 'R2R1',
-    'F F ', 'R F ', 'F R ', 'R R ', 'F1F2', 'R1F2', 'F1R2', 'R1R2',
     'F2F1', 'R2F1', 'F2R1', 'R2R1', 'F1F2', 'R1F2', 'F1R2', 'R1R2',
 ];
 const ASCII_CIGAR_CODES = [
@@ -18,10 +45,19 @@ const textDecoder = new TextDecoder();
 // Bitmask for ops that consume ref: M=0, D=2, N=3, P=6, ==7, X=8
 // Binary: 0b111001101 = 0x1CD
 const CIGAR_CONSUMES_REF_MASK = 0x1cd;
+function isNumericCigar(value) {
+    return (value instanceof Uint32Array ||
+        value instanceof Int32Array ||
+        Array.isArray(value));
+}
 // Decode a 'B' (array) tag value starting at `p` (the byte after type+subtype+
 // count). When the data is naturally aligned we return a typed-array view over
 // the underlying buffer (zero-copy); otherwise we copy element-by-element since
-// typed-array views require alignment. Shared by getTag and the full-tag parse.
+// typed-array views require alignment. The copy target is a plain array, not a
+// typed one: benchmarking the unaligned path found number[] fills faster below
+// ~10k elements and reads at least as fast at every size, so the only thing a
+// typed copy would buy is half the retained bytes. Shared by getTag and the
+// full-tag parse.
 function decodeBArrayTag(ba, dataView, p, Btype, limit) {
     const absOffset = ba.byteOffset + p;
     switch (Btype) {
@@ -312,7 +348,9 @@ export default class BamRecord {
     _computeTags() {
         const blockEnd = this._end;
         const ba = this._byteArray;
-        const tags = {};
+        // null prototype: tag names come from the file, so a read carrying a
+        // "constructor" or "toString" tag must not resolve to Object.prototype's
+        const tags = Object.create(null);
         let p = this.tagsStart;
         while (p < blockEnd) {
             const tag = String.fromCharCode(ba[p], ba[p + 1]);
@@ -409,6 +447,8 @@ export default class BamRecord {
         const absOffset = this._byteArray.byteOffset + p;
         if (absOffset % 4 === 0 && numCigarOps > 50) {
             const cigarView = new Uint32Array(this._byteArray.buffer, absOffset, numCigarOps);
+            // the view we need to sum is exactly what NUMERIC_CIGAR would build, so
+            // seed its cache rather than making it construct a second one
             this._cachedNumericCigar = cigarView;
             let lref = 0;
             for (let c = 0; c < numCigarOps; ++c) {
@@ -432,8 +472,10 @@ export default class BamRecord {
         const numCigarOps = flag_nc & 0xffff;
         const p = this.b0 + this.read_name_length;
         if (this._isCGTagPattern(p, numCigarOps)) {
-            return (this.tags.CG ??
-                new Uint32Array(0));
+            // getTag, not this.tags: the real CIGAR lives in one tag, so there's no
+            // reason to decode every other tag on the record to reach it
+            const cg = this.getTag('CG');
+            return isNumericCigar(cg) ? cg : new Uint32Array(0);
         }
         const absOffset = this._byteArray.byteOffset + p;
         if (absOffset % 4 === 0 && numCigarOps > 50) {
@@ -484,37 +526,65 @@ export default class BamRecord {
         const p = this.seqStart;
         return this._byteArray.subarray(p, p + this.num_seq_bytes);
     }
+    // Decode two bases per iteration off a 256-entry table. Building an array of
+    // 1-char strings and join()ing it — the obvious approach — is 3x slower at
+    // 100bp and 35x slower at 15kb.
     get seq() {
         const len = this.seq_length;
-        const seqStart = this.seqStart;
-        const numeric = this._byteArray;
-        const buf = new Array(len);
-        let i = 0;
-        const fullBytes = len >> 1;
-        for (let j = 0; j < fullBytes; ++j) {
-            const sb = numeric[seqStart + j];
-            buf[i++] = SEQRET_DECODER[(sb & 0xf0) >> 4];
-            buf[i++] = SEQRET_DECODER[sb & 0x0f];
-        }
-        if (i < len) {
-            const sb = numeric[seqStart + fullBytes];
-            buf[i] = SEQRET_DECODER[(sb & 0xf0) >> 4];
-        }
-        return buf.join('');
-    }
-    // adapted from igv.js
-    // uses precomputed lookup table indexed by flag bits + isize sign.
-    // the BAM spec defines tlen as positive for the leftmost segment and
-    // negative for the rightmost, so tlen > 0 reliably indicates which
-    // read comes first without needing position-based correction
+        const ba = this._byteArray;
+        const p = this.seqStart;
+        const nPairs = len >> 1;
+        let seq;
+        if (len < SEQ_DECODER_THRESHOLD) {
+            seq = '';
+            for (let j = 0; j < nPairs; j++) {
+                seq += SEQRET_PAIR_STRINGS[ba[p + j]];
+            }
+            if (len & 1) {
+                seq += SEQRET_DECODER[(ba[p + nPairs] & 0xf0) >> 4];
+            }
+        }
+        else {
+            // round up to an even length so the Uint16Array view spans every pair; a
+            // trailing odd base is written as a single byte and trimmed on decode
+            const out = new Uint8Array((len + 1) & ~1);
+            const pairs = new Uint16Array(out.buffer);
+            for (let j = 0; j < nPairs; j++) {
+                pairs[j] = SEQRET_PAIR_CODES[ba[p + j]];
+            }
+            if (len & 1) {
+                out[len - 1] = SEQRET_CODES[(ba[p + nPairs] & 0xf0) >> 4];
+            }
+            seq = textDecoder.decode(out.subarray(0, len));
+        }
+        return seq;
+    }
+    // Must come out identical from either mate, or the two halves of one normal
+    // pair render as different orientations. The leftmost mate is therefore picked
+    // by a total order on (refId, pos) that both mates evaluate the same way, with
+    // a read1-first tie-break for equal loci.
+    //
+    // Deriving "leftmost" from template_length looks tempting — the spec makes
+    // tlen positive for the leftmost segment and negative for the rightmost — but
+    // aligners leave tlen at 0 whenever the insert size is unavailable, which
+    // includes every cross-reference pair. Both mates then read as "not leftmost"
+    // and disagree with each other.
     // (see also: gmod/cram-js src/cramFile/record.ts getPairOrientation)
     get pair_orientation() {
         const f = this.flags;
-        // unmapped (0x4) or mate unmapped (0x8) -> undefined
-        if (f & 0xc || this.ref_id !== this.next_refid) {
+        if (!(f & Constants.BAM_FPAIRED)) {
             return undefined;
         }
-        return PAIR_ORIENTATION_TABLE[((f >> 4) & 0xf) | (this.template_length > 0 ? 16 : 0)];
+        const refId = this.ref_id;
+        const mateRefId = this.next_refid;
+        const pos = this.start;
+        const matePos = this.next_pos;
+        const selfIsLeft = refId !== mateRefId
+            ? refId < mateRefId
+            : pos !== matePos
+                ? pos < matePos
+                : !!(f & Constants.BAM_FREAD1);
+        return PAIR_ORIENTATION_TABLE[((f >> 4) & 0x7) | (selfIsLeft ? 8 : 0)];
     }
     get bin_mq_nl() {
         return this._dataView.getInt32(this._start + 12, true);
@@ -537,7 +607,7 @@ export default class BamRecord {
     seqAt(idx) {
         if (idx < this.seq_length) {
             const sb = this._byteArray[this.seqStart + (idx >> 1)];
-            return idx % 2 === 0
+            return (idx & 1) === 0
                 ? SEQRET_DECODER[(sb & 0xf0) >> 4]
                 : SEQRET_DECODER[sb & 0x0f];
         }