From 0a42a08591e1b854fb58c03d3a42269b5f45a330 Mon Sep 17 00:00:00 2001
From: Don Freed <donfreed12@gmail.com>
Date: Fri, 26 Sep 2025 15:41:33 -0700
Subject: [PATCH 1/3] Updates to variant grouping

- Remove `--maxdist` and replace it with a function that is dependent on the SV size
- Update the grouper to use a more sophisticated variant queue
- Add a tandem repeat (TR) bed input file. Variant groups that enter a TR region are automatically extended to the end of the tandem repeat.
---
 hap_eval/hap_eval.py | 179 +++++++++++++++++++++++++++++++++----------
 1 file changed, 139 insertions(+), 40 deletions(-)

diff --git a/hap_eval/hap_eval.py b/hap_eval/hap_eval.py
index 4744eb4..ad49ad4 100644
--- a/hap_eval/hap_eval.py
+++ b/hap_eval/hap_eval.py
@@ -3,6 +3,7 @@
 import argparse
 import bisect
 import collections
+from collections.abc import Callable
 import functools
 import heapq
 import io
@@ -11,6 +12,7 @@
 import os
 import re
 import sys
+from typing import Generator, Iterable, List, Tuple
 import tempfile
 import vcflib
 
@@ -133,20 +135,143 @@ def __contains__(self, cs):
         r = self.regions.get(c)
         return r and bisect.bisect_right(r, s) % 2 != 0
 
+def extend_event(
+    event_size: int,
+    base_extend: int = 20,
+    extend_frac: float = 0.2,
+    max_extend: int = 10000,
+) -> int:
+    '''Extension around events for grouping'''
+    return min(event_size * extend_frac + base_extend, max_extend)
+
+class VariantGroup(object):
+    '''A group of variants'''
+    def __init__(self, extend_func: Callable[[int], int]):
+        self.data: List[Tuple[int, vcflib.Variant]] = []
+        self.end = -1
+        self.end_extend = -1
+        self.extend_func = extend_func
+
+    def __iter__(self):
+        return iter(self.data)
+
+    def __bool__(self):
+        return bool(self.data)
+
+    def append(self, d: Tuple[int, vcflib.Variant]):
+        self.data.append(d)
+        self.end = max(self.end, d[1].end)
+        variant_size = max([len(x) for x in [d[1].ref] + d[1].alt])
+        extend_dist = self.extend_func(variant_size)
+        self.end_extend = max(self.end_extend, d[1].end + extend_dist)
+
+    def tr_extend(self, _tr_s: int, tr_e: int):
+        '''Extend the group across a tandem repeat'''
+        self.end = max(self.end, tr_e)
+
+class VariantGrouper(object):
+    '''Group variants from multiple VCFs by distance'''
+    def __init__(
+        self,
+        vcfs: Iterable[vcflib.VCF],
+        contig: str,
+        start: int,
+        end: int,
+        pred: Callable[[vcflib.Variant], bool],
+        extend_func: Callable[[int], int] = functools.partial(extend_event, base_extend=20, extend_frac=0.2, max_extend=10000),
+        tr_bed: IntervalList | None = None,
+    ):
+        self.vcfs = vcfs
+        self.contig = contig
+        self.start = start
+        self.end = end
+        self.pred = pred
+        self.tr_bed = tr_bed
+        self.extend_func = extend_func
+
+        self.maxdist = extend_func(999999999999)
+
+    def cluster(self) -> Generator[VariantGroup, None, None]:
+        '''Cluster variants in the VCF'''
+        q = []
+        for k, vcf in enumerate(self.vcfs):
+            if vcf is None:
+                continue
+            i = iter(vcf.range(self.contig, self.start-self.maxdist))
+            v = next(i, None)
+            while v and not self.pred(v):
+                v = next(i, None)
+            if v:
+                heapq.heappush(q, (v.pos, v.end, k, v, i))
+
+        p1: List[Tuple[int, int, int, vcflib.Variant]] = []
+        p2: List[Tuple[int, int, int, vcflib.Variant]] = []
+        g = VariantGroup(self.extend_func)
+        while q or p1:
+            if p1:
+                pos, end, k, v = p1.pop(0)
+            else:
+                pos, end, k, v, i = heapq.heappop(q)
+                v2 = next(i, None)
+                while v2 and not self.pred(v2):
+                    v2 = next(i, None)
+                if v2:
+                    heapq.heappush(q, (v2.pos, v2.end, k, v2, i))
+
+            if not g:
+                if pos >= self.end:
+                    break
+                else:
+                    g.append((k, v))
+                    # extend the group if overlapping a tandem repeat
+                    if self.tr_bed:
+                        tr_regions = self.tr_bed.get(self.contig, g.data[0][1].pos, g.end_extend)
+                        for tr_region in tr_regions:
+                            g.tr_extend(*tr_region)
+                    continue
+
+            variant_size = max([len(x) for x in [v.ref] + v.alt])
+            extend_dist = self.extend_func(variant_size)
+            if pos >= g.end + self.maxdist:
+                # This variant is too far from the group
+                if g and g.data[0][1].pos >= self.start and g.data[0][1].pos < self.end:
+                    yield g
+                g = VariantGroup(self.extend_func)
+                p1 = p2 + p1
+                p1.append((pos, end, k, v))
+                p2 = []
+            elif pos <= g.end_extend or g.end >= (pos - extend_dist):
+                # This variant is close enough to add to the group after the variants in the queue
+                for _, _, k2, v2 in p2:
+                    g.append((k2, v2))
+                p2 = []
+                g.append((k, v))
+
+                # extend the group if overlapping a tandem repeat
+                if self.tr_bed:
+                    tr_regions = self.tr_bed.get(self.contig, g.data[0][1].pos, g.end_extend)
+                    for tr_region in tr_regions:
+                        g.tr_extend(*tr_region)
+            else:
+                # This variant is an intermediate distance from the group, add to a queue
+                p2.append((pos, end, k, v))
+        if g and g.data[0][1].pos >= self.start and g.data[0][1].pos < self.end:
+            yield g
+
 class VCFEvaluator(vcflib.Shardable, vcflib.ShardResult):
     params = ( # name, defval, descr, kwargs
-        ('maxdist',     1000,   'Maximum distance to cluster variants', {}),
         ('minsize',     50,     'Minimum size of variants to consider', {}),
         ('maxdiff',     0.2,    'Haplotype difference theshold', {}),
         ('metric',      'Levenshtein',
             'Distance metric', {"choices": ['Levenshtein', 'Length']}),
     )
 
-    def __init__(self, ref, vcf1, vcf2, bed, args):
+    def __init__(self, ref, vcf1, vcf2, bed, tr_bed, args):
         self.ref = Reference(ref)
         self.vcf1 = vcflib.VCF(vcf1)
         self.vcf2 = vcflib.VCF(vcf2)
         self.bed = bed and IntervalList(bed) or None
+        self.tr_bed = tr_bed and IntervalList(tr_bed) or None
         self.args = args
         self.log = None
 
@@ -180,36 +305,6 @@ def add_arguments(cls, parser):
             h += ' (default: %(default)s)'
             parser.add_argument('--'+k, default=v, type=type(v), help=h, **kwargs)
 
-    @staticmethod
-    def cluster(vcfs, c, s, e, maxdist, pred):
-        q = []
-        for k, vcf in enumerate(vcfs):
-            if vcf is None:
-                continue
-            i = iter(vcf.range(c, s-maxdist))
-            v = next(i, None)
-            while v and not pred(v):
-                v = next(i, None)
-            if v:
-                heapq.heappush(q, (v.pos, v.end, k, v, i))
-        g = []
-        while q:
-            pos, end, k, v, i = heapq.heappop(q)
-            if g and pos >= g[-1][1].end + maxdist:
-                if g[0][1].pos >= s and g[0][1].pos < e:
-                    yield g
-                g = []
-                if pos >= e:
-                    break
-            g.append((k, v))
-            v = next(i, None)
-            while v and not pred(v):
-                v = next(i, None)
-            if v:
-                heapq.heappush(q, (v.pos, v.end, k, v, i))
-        if g and g[0][1].pos >= s and g[0][1].pos < e:
-            yield g
-
     @staticmethod
     def maxsize(g):
         sz = [0, 0]
@@ -283,10 +378,10 @@ def reassemble(c, s, e, r, g, ref):
         for b in itertools.product(*combos):
             if not b:
                 continue
-            h = [r] * len(b[0])
-            for j,p in enumerate(zip(*b)):
+            h = [r] * len(b[0])  # multiple haplotypes for diploid or polyploid samples
+            for j,p in enumerate(zip(*b)):  # j = haplotype index
                 t = s
-                for i in range(len(p)):
+                for i in range(len(p)):  # each variant allele
                     if p[i] == 0:
                         continue
                     v = g[i]
@@ -329,7 +424,7 @@ def diff_by_lev(a, b):
     def evaluate_cluster(
         g, contig, ref, diff, bed=None, maxdiff=0.2, minsize=50, log=sys.stdout
     ):
-        c, s, e = contig, g[0][1].pos, g[-1][1].end
+        c, s, e = contig, g.data[0][1].pos, g.end
         if bed and not bed.get(c, s, e):
             return None
         g0 = [x[1] for x in g if x[0] == 0]
@@ -419,8 +514,8 @@ def evaluate(
                     ' comparison.',
                     file=sys.stderr
                 )
-        maxdist = self.args.maxdist
-        for g in self.cluster(vcfs, contig, start, end, maxdist, pred):
+        grouper = VariantGrouper(vcfs, contig, start, end, pred, tr_bed=self.tr_bed)
+        for g in grouper.cluster():
             call = self.evaluate_cluster(
                 g,
                 contig,
@@ -436,7 +531,7 @@ def evaluate(
 
             g0 = [x[1] for x in g if x[0] == 0]
             g1 = [x[1] for x in g if x[0] == 1]
-            call_region = "{}:{}-{}".format(contig, g[0][1].pos, g[-1][1].end)
+            call_region = "{}:{}-{}".format(contig, g.data[0][1].pos, g.end)
             for out_vcf, g, err in zip(
                 (base_out, comp_out), (g0, g1), ('FN', 'FP')
             ):
@@ -470,6 +565,8 @@ def parse_args(argv=None):
         help='Comparison vcf file')
     parser.add_argument('-i', '--interval', required=False, metavar='BED',
         help='Evaluation region file', dest='bed')
+    parser.add_argument('--tr_bed', metavar='BED',
+        help='Tandem repeat BED file')
     parser.add_argument('-t', '--thread_count', required=False, type=int,
         help='Number of threads', dest='nthr')
     parser.add_argument('--base_out', metavar='VCF',
@@ -484,7 +581,9 @@ def parse_args(argv=None):
 
 def main():
     args = parse_args()
-    eval = VCFEvaluator(args.ref, args.base, args.comp, args.bed, args)
+    eval = VCFEvaluator(
+        args.ref, args.base, args.comp, args.bed, args.tr_bed, args
+    )
 
     out_vcfs = []
     for vcf, out_vcf in zip(

From bcfa8fd1c3fece1a1a8df5793c042c43a2e3b68d Mon Sep 17 00:00:00 2001
From: Don Freed <donfreed12@gmail.com>
Date: Fri, 26 Sep 2025 15:47:10 -0700
Subject: [PATCH 2/3] Add a tandem repeats bed file for hg38

This file was originally downloaded from the Tandem Repeats Database for hg38, "Homo sapiens HG38 (2,5,7,50, centr. excluded) Full Genome", sorted by chromosome and position. Basic filtering was applied to remove some repeats (size < 200 or match_perc < 80.5 or score < 300). The file was then converted to BED format and overlapping regions were merged.
---
 data/Homo_sapiens_HG38_tandem_repeats.bed | 66729 ++++++++++++++++++++
 1 file changed, 66729 insertions(+)
 create mode 100644 data/Homo_sapiens_HG38_tandem_repeats.bed

diff --git a/data/Homo_sapiens_HG38_tandem_repeats.bed b/data/Homo_sapiens_HG38_tandem_repeats.bed
new file mode 100644
index 0000000..03998e1
--- /dev/null
+++ b/data/Homo_sapiens_HG38_tandem_repeats.bed
@@ -0,0 +1,66729 @@
+chr1	10001	10468
+chr1	10758	10997
+chr1	66160	66630
+chr1	83788	84041
+chr1	88675	88962
+chr1	90048	90438
+chr1	136193	137288
+chr1	174382	174686
+chr1	180089	180998
+chr1	257667	258054
+chr1	361604	362236
+chr1	367153	367850
+chr1	368748	370063
+chr1	371669	372922
+chr1	373946	374164
+chr1	381155	381699
+chr1	382245	382632
+chr1	432583	434972
+chr1	492176	492490
+chr1	532977	533281
+chr1	596184	597016
+chr1	597795	598734
+chr1	600343	601176
+chr1	609341	610761
+chr1	611307	612522
+chr1	668335	669950
+chr1	727179	727396
+chr1	774791	775116
+chr1	788758	791673
+chr1	819914	823663
+chr1	839299	839650
+chr1	853416	853906
+chr1	866415	867192
+chr1	872504	873179
+chr1	875830	876438
+chr1	893506	894130
+chr1	904472	904744
+chr1	908921	909899
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+chr1	936235	936468
+chr1	960091	960472
+chr1	964543	964844
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+chr1	992884	993152
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+chr1	1002418	1002860
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+chr1	1017760	1018201
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+chr1	1029591	1031319
+chr1	1052454	1052929
+chr1	1056319	1056720
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+chr1	3361709	3362045
+chr1	3370789	3371610
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+chr1	3383800	3384203
+chr1	3408614	3408946
+chr1	3409647	3410190
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+chr1	3433420	3433647
+chr1	3470641	3471162
+chr1	3474901	3475800
+chr1	3493136	3493422
+chr1	3510320	3510654
+chr1	3546499	3546932
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From 71cb87c1cdd94d3fd6d376602d2c66d97bdd7a07 Mon Sep 17 00:00:00 2001
From: Don Freed <donfreed12@gmail.com>
Date: Fri, 26 Sep 2025 16:47:50 -0700
Subject: [PATCH 3/3] Update the README for the adaptive distance metric

---
 README.md | 67 ++++++++++++++++++-------------------------------------
 1 file changed, 22 insertions(+), 45 deletions(-)

diff --git a/README.md b/README.md
index a91cb34..e1ae7ed 100644
--- a/README.md
+++ b/README.md
@@ -26,19 +26,21 @@ optional arguments:
   -c VCF, --comp VCF    Comparison vcf file
   -i BED, --interval BED
                         Evaluation region file
+  --tr_bed BED          Tandem repeat BED file
   -t INT, --thread_count INT
                         Number of threads
   --base_out VCF        Annotated baseline vcf file
   --comp_out VCF        Annotated comparison vcf file
-  --maxdist INT         Maximum distance to cluster variants (default: 1000)
   --minsize INT         Minimum size of variants to consider (default: 50)
   --maxdiff FLOAT       Haplotype difference threshold (default: 0.2)
   --metric STR          Distance metric (default: Levenshtein)
 ```
 
-### Clustering, `--maxdist` and `--minsize`
+### Clustering, `--tr_bed`, and `--minsize`
 
-hap-eval evaluates groups (clusters) of variants that are nearby on the reference genome. Variants are grouped together if the distance between two variants is less than `--maxdist`. The entire group will be evaluated if the largest possible haplotype that can be constructed from the group has an insertion or deletion variant larger than `--minsize`.
+hap-eval evaluates groups (clusters) of variants that are nearby on the reference genome. Variants are grouped together if the distance between two variants is small relative to the variant size. If the variant group extends into a known tandem repeat (from the `--tr_bed` file), the group will be extended to the end of the tandem repeat. The entire group will be evaluated if the largest possible haplotype that can be constructed from the group has an insertion or deletion variant larger than `--minsize`.
+
+Using a `--tr_bed` bed file highly recommended as different structural variant callers may place structural variants at different locations along a tandem repeat. A tandem repeat bed file for hg38 is provided in the [/data](/data) directory.
 
 Some examples are shown below. For the purpose of demonstration, these examples use a baseline VCF (`--base`), but an empty comparison VCF `--comp`.
 
@@ -46,26 +48,23 @@ Some examples are shown below. For the purpose of demonstration, these examples
 
 The baseline VCF has the following variants:
 ```txt
-chr1    1541864 .       T       C       30      .       LCR=0   GT:AD   0|1:1,1
-chr1    1542773 .       T       C       30      .       LCR=0   GT:AD   0|1:1,1
-chr1    1542793 .       C       G       30      .       LCR=0   GT:AD   0|1:1,1
-chr1    1542800 .       T       C       30      .       LCR=0   GT:AD   0|1:1,1
-chr1    1543500 .       T       G       30      .       LCR=0   GT:AD   0|1:1,1
-chr1    1543725 .       C       CCTCTGTCACGGCCTCGGCCACTCCCCACTGTCACGGCCTCGGCCACTCCCCTCTGTCACGGCCTCGGCCACTCCCCTCTGTCACGGCCTCGGCCACTCCCCACTGTCACGGCCTCGGCCACTCCCCACTGTCACGGCCTCGGCCACTCCCCTCTGTCACGGCCTCGGCCACTCCCCACTGTCACGGCCTCGGCCACTCCCCT       30      .       TRF;TRFdiff=8.1;TRFrepeat=TCACGGCCTCGGCCACTCCCCTCTG;TRFovl=1;TRFstart=1543581;TRFend=1543840;TRFperiod=25;TRFcopies=18.7;TRFscore=672;TRFentropy=1.75;TRFsim=0.97;SVTYPE=INS;SVLEN=202;LCR=0.864133;REMAP=tandem        GT:AD   0|1:1,1
-chr1    1543953 .       A       G       30      .       LCR=0   GT:AD   0|1:1,1
+chr1    1948926 .       T       C       30      .       TRF;LCR=0       GT:AD   1|0:1,1
+chr1    1948934 .       T       TCCCTCCCTTCTTTCCTTCCCTTTCCCTCCCTCCCTTCCTTCCTCTTTCCTTCCTTCCTTTCCCTCCCTTACTCCTTCCTTCCTTCCCTTCCCCTTCCTTCTTCCTTCTCTC        30      .       TRF;TRFdiff=0;TRFrepeat=CCTTCCTTCCTTC;TRFovl=1;TRFstart=1948876;TRFend=1949289;TRFperiod=13;TRFcopies=32;TRFscore=633;TRFentropy=1.04;SVTYPE=INS;SVLEN=111;RM_score=35;RM_repeat=(TCCC)N;RM_clsfam=Simple_repeat;LCR=0.529985;REMAP=interspersed        GT:AD   1|0:1,1
+chr1    1948942 .       T       C       30      .       TRF;LCR=0       GT:AD   1|0:1,1
+chr1    1948947 .       T       C       30      .       TRF;LCR=0       GT:AD   1|0:1,1
 ```
 
-These variants are grouped together as they are all less than `--maxdist` (1000bp) from each other, evaluated as a single region by hap-eval, and contributed one `FN` to the overall evaluation (as there is no comparison VCF).
+These variants are grouped together as they are relatively close to the insertion allele. They are evaluated as a single region by hap-eval, and contributed one `FN` to the overall evaluation (as there is no comparison VCF).
 
 ```txt
-FN chr1:1541764-1544053 7 0 2290 (0,202) (0,0) 1.0
+FN chr1:1948826-1949047 4 0 222 (111,0) (0,0) 1.0
 ```
 
-#### Variants further than `--maxdist`
+#### Distant variants are not grouped
 
 The baseline VCF has the following variants:
 ```txt
-chr1    1981820 .       A       ACCGCGGACAGACACGGGGGCACGCAGGACACCCAGCCGCGGACAGACACGGGGGCACGCAGGACACCCAG         30      .       TRF;TRFdiff=2;TRFrepeat=ACACCCAGCCGCGGACAGACACGGGGGCACGCAGG;TRFovl=1;TRFstart=1981391;TRFend=1982440;TRFperiod=35;TRFcopies=31.9;TRFscore=2263;TRFentropy=1.71;TRFsim=1;SVTYPE=INS;SVLEN=70;LCR=0.785201;REMAP=tandem   GT:AD   1|1:0,2
+chr1    1981820 .       A       ACCGCGGACAGACACGGGGGCACGCAGGACACCCAGCCGCGGACAGACACGGGGGCACGCAGGACACCCAG 30      .       TRF;TRFdiff=2;TRFrepeat=ACACCCAGCCGCGGACAGACACGGGGGCACGCAGG;TRFovl=1;TRFstart=1981391;TRFend=1982440;TRFperiod=35;TRFcopies=31.9;TRFscore=2263;TRFentropy=1.71;TRFsim=1;SVTYPE=INS;SVLEN=70;LCR=0.785201;REMAP=tandem   GT:AD   1|1:0,2
 chr1    1986432 .       T       A       30      .       LCR=0   GT:AD   1|1:0,2
 chr1    1986564 .       G       A       30      .       LCR=0   GT:AD   0|1:1,1
 chr1    1991395 .       T       C       30      .       LCR=0   GT:AD   1|1:0,2
@@ -78,52 +77,30 @@ chr1    1991867 .       A       G       30      .       LCR=0   GT:AD   0|1:1,1
 chr1    1992226 .       A       G       30      .       LCR=0   GT:AD   1|1:0,2
 chr1    1992242 .       A       G       30      .       LCR=0   GT:AD   0|1:1,1
 chr1    1993704 .       A       AGGGCACAGTGGCTCATGCCTGTAATCCCAGCAACATGGGAGCCTGAGGTGGGAGGCTCTCTTGAGGCCAGGAGTTTGAGACCAGCCTGGGCAACATAGTGAGACCCCCCACCCCCCGCCATTTCTAGGAAAAAAAAAAAAAGTGGCC    30      .       SVTYPE=INS;SVLEN=147;RM_score=113;RM_repeat=FLAM_C;RM_clsfam=SINE/Alu;LCR=0.98366;REMAP=partial GT:AD   1|1:0,2
-chr1    1993887 .       C       A       30      .       LCR=0   GT:AD   1|1:0,2
-chr1    1993898 .       C       T       30      .       LCR=0   GT:AD   1|1:0,2
-chr1    1994025 .       C       T       30      .       LCR=0   GT:AD   1|1:0,2
-```
-
-These variants are split into two groups, as the distance between the variant at `chr1:1981820` and the variant at `chr1:1986432` greater than `--maxdist` (default 1000). Many of the SNVs are not included in either group.
-
-```txt
-FN chr1:1981720-1981920 1 0 201 (70,70) (0,0) 1.0
-FN chr1:1993604-1994125 4 0 522 (147,147) (0,0) 1.0
-```
-
-#### Grouping of deletions
-
-The baseline VCF has the following variants:
-```txt
-chr1    3643863 .       CGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACATGGGGTCGCGCCTTCGGAAGGGGATCCAGT C       30      .       TRF;TRFdiff=-10;TRFrepeat=TGGGGTCGCGCCTTCGGAAGGGGACCCAGCGGCCCCGCTGAGCCCCGGACA;TRFovl=1;TRFstart=3643528;TRFend=3644432;TRFperiod=51;TRFcopies=7.8;TRFscore=2578;TRFentropy=1.8;SVTYPE=DEL;SVLEN=510;LCR=0.894375;REMAP=tandem   GT:AD   1|1:0,2
-chr1    3645341 .       AGCGGCGCAGCGGGATGGGCGGGTTGCCCCGTGGTGTGCGTGGCGCAGCGGGACGGGCGGGTTGCCCCGTGGTGTGC   A       30      .       TRF;TRFdiff=-2;TRFrepeat=CGTGGTGTGCGCGGCGCAGCGGGACGGGCGGGTTGCCC;TRFovl=1;TRFstart=3645293;TRFend=3645554;TRFperiod=38;TRFcopies=4.9;TRFscore=666;TRFentropy=1.66;SVTYPE=DEL;SVLEN=76;LCR=0.83505;REMAP=tandem   GT:AD   1|1:0,2
-chr1    3645458 .       C       G       30      .       TRF;LCR=0       GT:AD   1|1:0,2
-chr1    3645460 .       T       C       30      .       TRF;LCR=0       GT:AD   1|1:0,2
-chr1    3646061 .       C       G       30      .       LCR=0   GT:AD   0|1:1,1
 ```
 
-The first deletion extends 510bp over the reference genome. This extension allows the two deletions to be grouped, even if `chr1:3645341` is more than `--maxdist` from `chr1:3643863`.
+These variants are split into two groups, as the distance between the variant at `chr1:1981820` and the variant at `chr1:1993704` is relatively large and the insertions are relatively small. The intervening SNVs are not included in either group.
 
 ```txt
-FN chr1:3643763-3646161 5 0 2399 (-586,-586) (0,0) 1.0
+FN chr1:1981720-1982541 1 0 822 (70,70) (0,0) 1.0
+FN chr1:1993604-1993804 1 0 201 (147,147) (0,0) 1.0
 ```
 
 #### Multiple variants exceeding `--minsize`
 
 The baseline VCF has the following variants:
 ```txt
-chr1    5700440 .       A       G       30      .       LCR=0   GT:AD   1|1:0,2
-chr1    5700987 .       A       T       30      .       LCR=0   GT:AD   1|1:0,2
-chr1    5701753 .       G       GAGAGAAAGAAAGAAAGAAAGAAAGAAAGAAAGAA     30      .       TRF;TRFdiff=0;TRFrepeat=GAAA;TRFovl=1;TRFstart=5701732;TRFend=5701949;TRFperiod=4;TRFcopies=54.2;TRFscore=297;TRFentropy=1.01;SVTYPE=INS;SVLEN=34;RM_score=34;RM_repeat=(AGAA)N;RM_clsfam=Simple_repeat;LCR=0.43156;REMAP=interspersed  GT:AD   1|1:0,2
-chr1    5701872 .       G       GAGGGAGGAAGGAAGGAAGGA   30      .       TRF;TRFdiff=5;TRFrepeat=GAAG;TRFovl=1;TRFstart=5701732;TRFend=5701921;TRFperiod=4;TRFcopies=50;TRFscore=226;TRFentropy=1.06;TRFsim=0.925;SVTYPE=INS;SVLEN=20;LCR=0.492614;REMAP=interspersed    GT:AD   0|1:1,1
-chr1    5701908 .       A       AAGGAAGGAAGGAAGGAAGGAAGGAAGGG   30      .       TRF;TRFdiff=7;TRFrepeat=GAAG;TRFovl=1;TRFstart=5701732;TRFend=5701921;TRFperiod=4;TRFcopies=52;TRFscore=226;TRFentropy=1.06;TRFsim=0.946;SVTYPE=INS;SVLEN=28;RM_score=30;RM_repeat=(AAGG)N;RM_clsfam=Simple_repeat;LCR=0.499571;REMAP=interspersed      GT:AD   1|0:0,1
-chr1    5701908 .       A       G       30      .       TRF;LCR=0       GT:AD   0|1:0,1
-chr1    5702582 .       G       A       30      .       LCR=0   GT:AD   1|0:1,1
+chr1    16166161        .       G       GCCATCCATCCAGCCATCCAT   30      .       TRF;TRFdiff=0;TRFrepeat=TCCA;TRFovl=1;TRFstart=16166148;TRFend=16166283;TRFperiod=4;TRFcopies=33.8;TRFscore=325;TRFentropy=1.65;SVTYPE=INS;SVLEN=20;LCR=0.890708;REMAP=interspersed     GT:AD   1|0:1,1
+chr1    16166181        .       T       G       30      .       TRF;LCR=0       GT:AD   1|0:0,1
+chr1    16166181        .       TCCATCCATCCATCCATCCAG   T       30      .       TRF;TRFdiff=-2.5;TRFrepeat=TCCCTCCT;TRFovl=1;TRFstart=16166164;TRFend=16166283;TRFperiod=8;TRFcopies=12.6;TRFscore=73;TRFentropy=1.6;SVTYPE=DEL;SVLEN=20;LCR=0.852383;REMAP=interspersed        GT:AD   0|1:0,1
+chr1    16166229        .       T       TCCATCCATCCATCCATCCATCCATCCAGCCATCCATCCATCCATCCAG       30      .
+       TRF;TRFdiff=0;TRFrepeat=TCCA;TRFovl=1;TRFstart=16166148;TRFend=16166311;TRFperiod=4;TRFcopies=40.8;TRFscore=399;TRFentropy=1.65;SVTYPE=INS;SVLEN=48;RM_score=48;RM_repeat=(TCCA)N;RM_clsfam=Simple_repeat;LCR=0.83682;REMAP=tandem      GT:AD   1|0:1,1
 ```
 
 Individually, each of these variants is smaller than `--minsize`. However, they can be combined together into a haplotype larger than `--minsize`. Accordingly, they are evaluated as a group by hap-eval.
 
 ```txt
-FN chr1:5700340-5702682 7 0 2343 (62,54) (0,0) 1.0
+FN chr1:16166061-16166329 4 0 269 (68,-20) (0,0) 1.0
 ```
 
 #### Variants less than `--minsize`