@gmod/gbz-base 2.0.0 → 2.1.0

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Files changed (10) hide show
  1. package/README.md +17 -6
  2. package/dist/db.js +5 -0
  3. package/dist/db.js.map +1 -1
  4. package/dist/subgraph.d.ts +3 -1
  5. package/dist/subgraph.js +60 -23
  6. package/dist/subgraph.js.map +1 -1
  7. package/package.json +1 -1
  8. package/src/db.ts +7 -0
  9. package/src/subgraph.ts +60 -24
  10. package/tools/haplotype-index/src/main.rs +20 -11
package/README.md CHANGED
@@ -78,10 +78,12 @@ for (const alignment of alignments) {
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  They run to node boundaries, so a record can begin before the window you asked
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  for and end after it. `cigar` is its alignment to that reference, computed like
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  upstream: a node-length-weighted LCS, with the diverging stretches scored using
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- vg's match, mismatch and gap parameters. `path` is the walk as node handles,
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- `weight` is how many identical haplotypes it stands for, and `start` is its GBWT
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- position, which is a property of the graph and so is stable across refetches of
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- the same window.
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+ vg's match, mismatch and gap parameters. `strand` is `-` when the haplotype runs
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+ through the window in the opposite direction to the reference, so the same pair
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+ of paths reports the same strand whichever of the two is the reference. `path`
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+ is the walk as node handles, `weight` is how many identical haplotypes it stands
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+ for, and `start` is its GBWT position, which is a property of the graph and so
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+ is stable across refetches of the same window.
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  Naming a fragment needs the haplotype index described below, and a database
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  without one cannot do it, so the record is a union on `resolved` rather than a
@@ -190,8 +192,8 @@ const db = await GBZBase.open(new RemoteFile(graphUrl), {
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  This is how a database someone else publishes gets haplotype names without
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  anyone rehosting it: HPRC publishes `hprc-v2.1-mc-grch38.gbz.db` (10 GB) beside
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  its graphs, and the companion for it is built from the 5 GB GBZ. The companion
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- records the graph's path count and the reader refuses one built for a different
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- graph.
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+ records the graph's path and node counts and the reader refuses one built for a
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+ different graph.
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  `HaplotypeSamples` holds one GBWT position every `--interval` bp along every
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  path in both orientations, with the path handle and the forward coordinate of
@@ -240,6 +242,15 @@ node can be placed in order; the Myers-based weighted LCS from gbwt-rs runs only
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  for the fragments where that fails (inversions, repeats). The two can pick
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  different equal-weight alignments only when the reference walk repeats a node.
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+ One deliberate departure: where a reference walk is stored against node
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+ orientation (upstream prints "the reference path is not in canonical
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+ orientation" there), every other walk comes out in the opposite orientation, and
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+ upstream aligns them handle for handle, giving all-insertion CIGARs against the
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+ reference despite the nodes being shared. This reader aligns each walk in
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+ whichever orientation shares more sequence with the reference and reports `-` on
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+ such records. CHM13 on HPRC chr20 has one such region, right after the fragment
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+ starting at 30368374.
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+
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  ## Measured
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  Against a 134 MB HPRC chr20 `.gbz.db` served over HTTPS,
package/dist/db.js CHANGED
@@ -131,6 +131,11 @@ export class GBZBase {
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  if (indexed !== paths) {
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  throw new Error(`haplotype index was built for ${indexed ?? 'an unknown number of'} paths but the graph has ${paths}`);
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  }
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+ const indexedNodes = db.indexTags.get('haplotype_index_nodes');
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+ const nodes = await db.tag('nodes');
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+ if (indexedNodes !== undefined && indexedNodes !== nodes) {
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+ throw new Error(`haplotype index was built for a graph with ${indexedNodes} nodes but this one has ${nodes}`);
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+ }
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  }
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  return db;
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  }
package/dist/db.js.map CHANGED
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package/dist/subgraph.d.ts CHANGED
@@ -135,7 +135,9 @@ export declare class Subgraph {
135
135
  private prefixMatches;
136
136
  private suffixMatches;
137
137
  private align;
138
- private edits;
138
+ private sharedWeight;
139
+ private editsAgainst;
140
+ private alignment;
139
141
  alignToRef(pathIndex: number): string | undefined;
140
142
  alignments(): HaplotypeAlignment[];
141
143
  private canonicalEdges;
package/dist/subgraph.js CHANGED
@@ -833,13 +833,18 @@ export class Subgraph {
833
833
  }
834
834
  appendEdit(edits, 'M', suffix);
835
835
  }
836
- edits(pathIndex) {
837
- const info = this.paths[pathIndex];
838
- if (this.refId === undefined || pathIndex === this.refId || !info) {
839
- return undefined;
836
+ sharedWeight(path, ref) {
837
+ const index = this.refIndex(ref);
838
+ let weight = 0;
839
+ for (const handle of path) {
840
+ if (index.has(handle)) {
841
+ weight += this.record(handle).sequenceLen;
842
+ }
840
843
  }
841
- const ref = this.paths[this.refId].path;
842
- const ordered = this.orderedMatches(info.path, ref);
844
+ return weight;
845
+ }
846
+ editsAgainst(path, ref) {
847
+ const ordered = this.orderedMatches(path, ref);
843
848
  if (ordered) {
844
849
  this.stats.orderedAlignments += 1;
845
850
  }
@@ -847,22 +852,59 @@ export class Subgraph {
847
852
  this.stats.lcsAlignments += 1;
848
853
  }
849
854
  const lcs = ordered ??
850
- weightedLcs(info.path, ref, handle => this.record(handle).sequenceLen)[0];
855
+ weightedLcs(path, ref, handle => this.record(handle).sequenceLen)[0];
851
856
  const edits = [];
857
+ let matched = 0;
852
858
  let pathOffset = 0;
853
859
  let refOffset = 0;
854
860
  for (const [nextPath, nextRef] of lcs) {
855
- this.align(info.path.slice(pathOffset, nextPath), ref.slice(refOffset, nextRef), edits);
856
- appendEdit(edits, 'M', this.record(info.path[nextPath]).sequenceLen);
861
+ this.align(path.slice(pathOffset, nextPath), ref.slice(refOffset, nextRef), edits);
862
+ const nodeLen = this.record(path[nextPath]).sequenceLen;
863
+ appendEdit(edits, 'M', nodeLen);
864
+ matched += nodeLen;
857
865
  pathOffset = nextPath + 1;
858
866
  refOffset = nextRef + 1;
859
867
  }
860
- this.align(info.path.slice(pathOffset), ref.slice(refOffset), edits);
861
- return edits;
868
+ this.align(path.slice(pathOffset), ref.slice(refOffset), edits);
869
+ return { edits, matched };
870
+ }
871
+ alignment(pathIndex) {
872
+ const info = this.paths[pathIndex];
873
+ if (this.refId === undefined || pathIndex === this.refId || !info) {
874
+ return undefined;
875
+ }
876
+ const ref = this.paths[this.refId].path;
877
+ const flippedPath = pathIsCanonical(ref)
878
+ ? []
879
+ : info.path.map(handle => flipNode(handle)).reverse();
880
+ const forwardBound = this.sharedWeight(info.path, ref);
881
+ const flippedBound = this.sharedWeight(flippedPath, ref);
882
+ let result;
883
+ if (flippedBound === 0) {
884
+ result = {
885
+ edits: this.editsAgainst(info.path, ref).edits,
886
+ flipped: false,
887
+ };
888
+ }
889
+ else if (forwardBound === 0) {
890
+ result = {
891
+ edits: this.editsAgainst(flippedPath, ref).edits,
892
+ flipped: true,
893
+ };
894
+ }
895
+ else {
896
+ const forward = this.editsAgainst(info.path, ref);
897
+ const flipped = this.editsAgainst(flippedPath, ref);
898
+ result =
899
+ flipped.matched > forward.matched
900
+ ? { edits: flipped.edits, flipped: true }
901
+ : { edits: forward.edits, flipped: false };
902
+ }
903
+ return result;
862
904
  }
863
905
  alignToRef(pathIndex) {
864
- return this.edits(pathIndex)
865
- ?.map(([op, len]) => `${len}${op}`)
906
+ return this.alignment(pathIndex)
907
+ ?.edits.map(([op, len]) => `${len}${op}`)
866
908
  .join('');
867
909
  }
868
910
  alignments() {
@@ -877,7 +919,7 @@ export class Subgraph {
877
919
  if (index === this.refId) {
878
920
  return;
879
921
  }
880
- const edits = this.edits(index);
922
+ const { edits, flipped } = this.alignment(index);
881
923
  let first = 0;
882
924
  let leading = 0;
883
925
  while (first < edits.length && edits[first][0] === 'D') {
@@ -891,16 +933,11 @@ export class Subgraph {
891
933
  last -= 1;
892
934
  }
893
935
  const identity = info.identity;
894
- const walkStrand = info.path.some(handle => isReverse(handle)) &&
895
- !info.path.some(handle => !isReverse(handle))
896
- ? '-'
897
- : '+';
936
+ const alongReference = identity
937
+ ? (identity.orientation === 'forward') !== flipped
938
+ : !flipped;
898
939
  const span = {
899
- strand: identity
900
- ? identity.orientation === 'forward'
901
- ? '+'
902
- : '-'
903
- : walkStrand,
940
+ strand: alongReference ? '+' : '-',
904
941
  refStart: reference.start + leading,
905
942
  refEnd: reference.start + refTotal - trailing,
906
943
  cigar: edits
package/dist/subgraph.js.map CHANGED
@@ -1 +1 @@
1
- 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package/package.json CHANGED
@@ -1,6 +1,6 @@
1
1
  {
2
2
  "name": "@gmod/gbz-base",
3
- "version": "2.0.0",
3
+ "version": "2.1.0",
4
4
  "description": "Pure TypeScript reader for gbz-base pangenome databases (.gbz.db) with random access over HTTP range requests",
5
5
  "license": "MIT",
6
6
  "packageManager": "pnpm@11.15.1",
package/src/db.ts CHANGED
@@ -196,6 +196,13 @@ export class GBZBase {
196
196
  `haplotype index was built for ${indexed ?? 'an unknown number of'} paths but the graph has ${paths}`,
197
197
  )
198
198
  }
199
+ const indexedNodes = db.indexTags.get('haplotype_index_nodes')
200
+ const nodes = await db.tag('nodes')
201
+ if (indexedNodes !== undefined && indexedNodes !== nodes) {
202
+ throw new Error(
203
+ `haplotype index was built for a graph with ${indexedNodes} nodes but this one has ${nodes}`,
204
+ )
205
+ }
199
206
  }
200
207
  return db
201
208
  }
package/src/subgraph.ts CHANGED
@@ -1045,13 +1045,19 @@ export class Subgraph {
1045
1045
  appendEdit(edits, 'M', suffix)
1046
1046
  }
1047
1047
 
1048
- private edits(pathIndex: number): Edit[] | undefined {
1049
- const info = this.paths[pathIndex]
1050
- if (this.refId === undefined || pathIndex === this.refId || !info) {
1051
- return undefined
1048
+ private sharedWeight(path: number[], ref: number[]) {
1049
+ const index = this.refIndex(ref)
1050
+ let weight = 0
1051
+ for (const handle of path) {
1052
+ if (index.has(handle)) {
1053
+ weight += this.record(handle).sequenceLen
1054
+ }
1052
1055
  }
1053
- const ref = this.paths[this.refId]!.path
1054
- const ordered = this.orderedMatches(info.path, ref)
1056
+ return weight
1057
+ }
1058
+
1059
+ private editsAgainst(path: number[], ref: number[]) {
1060
+ const ordered = this.orderedMatches(path, ref)
1055
1061
  if (ordered) {
1056
1062
  this.stats.orderedAlignments += 1
1057
1063
  } else {
@@ -1059,27 +1065,63 @@ export class Subgraph {
1059
1065
  }
1060
1066
  const lcs =
1061
1067
  ordered ??
1062
- weightedLcs(info.path, ref, handle => this.record(handle).sequenceLen)[0]
1068
+ weightedLcs(path, ref, handle => this.record(handle).sequenceLen)[0]
1063
1069
  const edits: Edit[] = []
1070
+ let matched = 0
1064
1071
  let pathOffset = 0
1065
1072
  let refOffset = 0
1066
1073
  for (const [nextPath, nextRef] of lcs) {
1067
1074
  this.align(
1068
- info.path.slice(pathOffset, nextPath),
1075
+ path.slice(pathOffset, nextPath),
1069
1076
  ref.slice(refOffset, nextRef),
1070
1077
  edits,
1071
1078
  )
1072
- appendEdit(edits, 'M', this.record(info.path[nextPath]!).sequenceLen)
1079
+ const nodeLen = this.record(path[nextPath]!).sequenceLen
1080
+ appendEdit(edits, 'M', nodeLen)
1081
+ matched += nodeLen
1073
1082
  pathOffset = nextPath + 1
1074
1083
  refOffset = nextRef + 1
1075
1084
  }
1076
- this.align(info.path.slice(pathOffset), ref.slice(refOffset), edits)
1077
- return edits
1085
+ this.align(path.slice(pathOffset), ref.slice(refOffset), edits)
1086
+ return { edits, matched }
1087
+ }
1088
+
1089
+ private alignment(pathIndex: number) {
1090
+ const info = this.paths[pathIndex]
1091
+ if (this.refId === undefined || pathIndex === this.refId || !info) {
1092
+ return undefined
1093
+ }
1094
+ const ref = this.paths[this.refId]!.path
1095
+ const flippedPath = pathIsCanonical(ref)
1096
+ ? []
1097
+ : info.path.map(handle => flipNode(handle)).reverse()
1098
+ const forwardBound = this.sharedWeight(info.path, ref)
1099
+ const flippedBound = this.sharedWeight(flippedPath, ref)
1100
+ let result: { edits: Edit[]; flipped: boolean }
1101
+ if (flippedBound === 0) {
1102
+ result = {
1103
+ edits: this.editsAgainst(info.path, ref).edits,
1104
+ flipped: false,
1105
+ }
1106
+ } else if (forwardBound === 0) {
1107
+ result = {
1108
+ edits: this.editsAgainst(flippedPath, ref).edits,
1109
+ flipped: true,
1110
+ }
1111
+ } else {
1112
+ const forward = this.editsAgainst(info.path, ref)
1113
+ const flipped = this.editsAgainst(flippedPath, ref)
1114
+ result =
1115
+ flipped.matched > forward.matched
1116
+ ? { edits: flipped.edits, flipped: true }
1117
+ : { edits: forward.edits, flipped: false }
1118
+ }
1119
+ return result
1078
1120
  }
1079
1121
 
1080
1122
  alignToRef(pathIndex: number) {
1081
- return this.edits(pathIndex)
1082
- ?.map(([op, len]) => `${len}${op}`)
1123
+ return this.alignment(pathIndex)
1124
+ ?.edits.map(([op, len]) => `${len}${op}`)
1083
1125
  .join('')
1084
1126
  }
1085
1127
 
@@ -1095,7 +1137,7 @@ export class Subgraph {
1095
1137
  if (index === this.refId) {
1096
1138
  return
1097
1139
  }
1098
- const edits = this.edits(index)!
1140
+ const { edits, flipped } = this.alignment(index)!
1099
1141
  let first = 0
1100
1142
  let leading = 0
1101
1143
  while (first < edits.length && edits[first]![0] === 'D') {
@@ -1109,17 +1151,11 @@ export class Subgraph {
1109
1151
  last -= 1
1110
1152
  }
1111
1153
  const identity = info.identity
1112
- const walkStrand =
1113
- info.path.some(handle => isReverse(handle)) &&
1114
- !info.path.some(handle => !isReverse(handle))
1115
- ? '-'
1116
- : '+'
1154
+ const alongReference = identity
1155
+ ? (identity.orientation === 'forward') !== flipped
1156
+ : !flipped
1117
1157
  const span: AlignmentSpan = {
1118
- strand: identity
1119
- ? identity.orientation === 'forward'
1120
- ? '+'
1121
- : '-'
1122
- : walkStrand,
1158
+ strand: alongReference ? '+' : '-',
1123
1159
  refStart: reference.start + leading,
1124
1160
  refEnd: reference.start + refTotal - trailing,
1125
1161
  cigar: edits
package/tools/haplotype-index/src/main.rs CHANGED
@@ -21,7 +21,8 @@ HaplotypeLengths. The path start and end are always sampled.
21
21
  By default the tables are written into the database itself, replacing any
22
22
  existing ones. With --output FILE they are written into FILE as a standalone
23
23
  companion database that the reader opens beside the graph database; the
24
- companion records the graph's path count so a mismatch is caught at open.
24
+ companion records the graph's path and node counts so a mismatch is caught at
25
+ open.
25
26
 
26
27
  With --from-db the walk reads node records from the database itself, so the
27
28
  GBZ is not needed. Walking a GBZ uses --threads (default: all cores).
@@ -269,7 +270,7 @@ CREATE TABLE HaplotypeLengths (
269
270
  length INTEGER NOT NULL
270
271
  ) STRICT;";
271
272
 
272
- fn write(target: &str, standalone: bool, mut samples: Vec<Sample>, lengths: &[(usize, usize)], paths: usize, args: &Args) {
273
+ fn write(target: &str, standalone: bool, mut samples: Vec<Sample>, lengths: &[(usize, usize)], paths: usize, nodes: usize, args: &Args) {
273
274
  let started = Instant::now();
274
275
  samples.sort_unstable_by_key(|s| (s.node_handle, s.node_offset));
275
276
  eprintln!("Sorted {} samples in {:.0} s", samples.len(), started.elapsed().as_secs_f64());
@@ -302,22 +303,23 @@ fn write(target: &str, standalone: bool, mut samples: Vec<Sample>, lengths: &[(u
302
303
  write_tag.execute(params!["haplotype_index_interval", args.interval.to_string()]).unwrap();
303
304
  write_tag.execute(params!["haplotype_index_orientations", if args.forward_only { "forward" } else { "both" }]).unwrap();
304
305
  write_tag.execute(params!["haplotype_index_paths", paths.to_string()]).unwrap();
306
+ write_tag.execute(params!["haplotype_index_nodes", nodes.to_string()]).unwrap();
305
307
  }
306
308
  transaction.commit().unwrap();
307
309
  eprintln!("Wrote {} samples for {} paths to {} in {:.0} s", samples.len(), paths, target, started.elapsed().as_secs_f64());
308
310
  }
309
311
 
310
- fn path_count_from_db(db: &str) -> usize {
312
+ fn count_from_db(db: &str, key: &str) -> usize {
311
313
  let connection = Connection::open(db).unwrap();
312
314
  let value: String = connection
313
- .query_row("SELECT value FROM Tags WHERE key = 'paths'", [], |row| row.get(0))
315
+ .query_row("SELECT value FROM Tags WHERE key = ?1", params![key], |row| row.get(0))
314
316
  .unwrap_or_else(|_| "0".to_string());
315
317
  value.parse().unwrap_or(0)
316
318
  }
317
319
 
318
320
  fn main() {
319
321
  let args = parse_args();
320
- let (samples, lengths, paths) = match &args.gbz {
322
+ let (samples, lengths, paths, nodes) = match &args.gbz {
321
323
  Some(gbz) => {
322
324
  let started = Instant::now();
323
325
  let graph: GBZ = serialize::load_from(gbz).unwrap_or_else(|e| {
@@ -330,19 +332,26 @@ fn main() {
330
332
  process::exit(1);
331
333
  }
332
334
  eprintln!("Loaded {} with {} paths in {:.0} s", gbz, paths, started.elapsed().as_secs_f64());
335
+ let nodes = graph.nodes();
333
336
  if let Some(db) = &args.db {
334
- let db_paths = path_count_from_db(db);
337
+ let db_paths = count_from_db(db, "paths");
335
338
  if db_paths != paths {
336
339
  eprintln!("{} has {} paths but {} has {}", gbz, paths, db, db_paths);
337
340
  process::exit(1);
338
341
  }
342
+ let db_nodes = count_from_db(db, "nodes");
343
+ if db_nodes != nodes {
344
+ eprintln!("{} has {} nodes but {} has {}", gbz, nodes, db, db_nodes);
345
+ process::exit(1);
346
+ }
339
347
  }
340
348
  let (samples, lengths) = walk_gbz(&graph, paths, &args);
341
- (samples, lengths, paths)
349
+ (samples, lengths, paths, nodes)
342
350
  }
343
351
  None => {
344
352
  let db = args.db.as_ref().unwrap();
345
- let paths = path_count_from_db(db);
353
+ let paths = count_from_db(db, "paths");
354
+ let nodes = count_from_db(db, "nodes");
346
355
  let database = GBZBase::open(db).unwrap_or_else(|e| {
347
356
  eprintln!("Cannot open {} as a GBZ-base: {}", db, e);
348
357
  process::exit(1);
@@ -350,12 +359,12 @@ fn main() {
350
359
  let interface = GraphInterface::new(&database).unwrap();
351
360
  let source = DbSource { interface: std::cell::RefCell::new(interface) };
352
361
  let (samples, lengths) = walk_paths(&source, 0..paths, &args, "database walk");
353
- (samples, lengths, paths)
362
+ (samples, lengths, paths, nodes)
354
363
  }
355
364
  };
356
365
  match (&args.output, &args.db) {
357
- (Some(output), _) => write(output, true, samples, &lengths, paths, &args),
358
- (None, Some(db)) => write(db, false, samples, &lengths, paths, &args),
366
+ (Some(output), _) => write(output, true, samples, &lengths, paths, nodes, &args),
367
+ (None, Some(db)) => write(db, false, samples, &lengths, paths, nodes, &args),
359
368
  (None, None) => unreachable!(),
360
369
  }
361
370
  }