feat: Add longtr support

doc/CALLERS.rst

@@ -3,7 +3,7 @@
 Supported TR Genotypers
 =======================
 
-TRTools currently supports 5 tandem repeat genotypers. It also supports the Beagle imputation software (see :ref:`below <Beagle_section>`).
+TRTools currently supports 6 tandem repeat genotypers. It also supports the Beagle imputation software (see :ref:`below <Beagle_section>`).
 We summarize them in the first table and provide some basic parameters of their functionality in the second.
 For more information on a genotyper, please see its website linked below.
 
@@ -39,6 +39,9 @@ For more information on a genotyper, please see its website linked below.
 |    PopSTR_ (v2.0)          | Designed for genome-wide genotyping  |
 |                            | of short or expanded TRs.            |
 +----------------------------+--------------------------------------+
+|    LongTR_ (v1.0)          | Designed for genome-wide genotyping  |
+|                            | of STRs and VNTRs from long reads.   |
++----------------------------+--------------------------------------+
 
 |
 
@@ -58,6 +61,8 @@ For more information on a genotyper, please see its website linked below.
 +----------------------------+--------------------------+----------------------------+------------------------+--------------------------+-------------------------+------------------------+
 |    PopSTR_ (v2.0)          | 1-6bp                    | Yes                        | Length                 | 540,1401 (hg38)          | Illumina                | Many                   |
 +----------------------------+--------------------------+----------------------------+------------------------+--------------------------+-------------------------+------------------------+
+|    LongTR_ (v1.0)          | 1+bp                     | No                         | Length, sequence       | No ref provided          | PacBio HiFi, ONT        | Many                   |
++----------------------------+--------------------------+----------------------------+------------------------+--------------------------+-------------------------+------------------------+
 
 Since each of these tools take as input a list of TRs to genotype, they could also be used on custom panels of TR loci.
 Tool information and reference panel numbers shown above are based on downloads from the github repository of each tool as of July 2, 2020.
@@ -74,6 +79,7 @@ see :ref:`Contributing` for more information.
 .. _GangSTR: https://github.com/gymreklab/gangstr
 .. _HipSTR: https://hipstr-tool.github.io/HipSTR/
 .. _PopSTR: https://github.com/DecodeGenetics/popSTR
+.. _LongTR: https://github.com/gymrek-lab/longtr
 
 .. _Beagle_section:
 

doc/index.rst

@@ -121,17 +121,19 @@ TRTools supports VCFs from the following TR genotyping tools:
 * GangSTR_ version 2.4 or higher
 * HipSTR [`main repo <https://github.com/tfwillems/HipSTR>`_] [`Gymrek Lab repo <https://github.com/gymrek-lab/hipstr>`_]
 * PopSTR_ version 2 or higher
+* LongTR_
 
 See our description of the :doc:`features and example use-cases </CALLERS>` of each of these tools.
 
 ..
-    please ensure this list of links remains the same as the one in the main README
+    please ensure this list of links remains the same as the one in CALLERS.rst
 
 .. _AdVNTR: https://advntr.readthedocs.io
 .. _ExpansionHunter: https://github.com/Illumina/ExpansionHunter
 .. _GangSTR: https://github.com/gymreklab/gangstr
 .. _HipSTR: https://hipstr-tool.github.io/HipSTR/
 .. _PopSTR: https://github.com/DecodeGenetics/popSTR
+.. _LongTR: https://github.com/gymrek-lab/longtr
 
 Testing
 -------

test/cmdline_tests.sh

@@ -119,6 +119,7 @@ runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_gangstr.sorted.vcf.gz --ou
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_gangstr.sorted.vcf.gz --out stdout --mean --vcftype eh"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_gangstr.sorted.vcf.gz --out stdout --mean --vcftype advntr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_gangstr.sorted.vcf.gz --out stdout --mean --vcftype popstr"
+runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_gangstr.sorted.vcf.gz --out stdout --mean --vcftype longtr"
 
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_hipstr.sorted.vcf.gz --out stdout --mean --vcftype gangstr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_hipstr.sorted.vcf.gz --out stdout --mean --vcftype eh"
@@ -129,16 +130,20 @@ runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_eh.sorted.vcf.gz --out std
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_eh.sorted.vcf.gz --out stdout --mean --vcftype hipstr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_eh.sorted.vcf.gz --out stdout --mean --vcftype advntr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_eh.sorted.vcf.gz --out stdout --mean --vcftype popstr"
+runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_eh.sorted.vcf.gz --out stdout --mean --vcftype longtr"
 
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_popstr.sorted.vcf.gz --out stdout --mean --vcftype gangstr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_popstr.sorted.vcf.gz --out stdout --mean --vcftype hipstr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_popstr.sorted.vcf.gz --out stdout --mean --vcftype advntr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_popstr.sorted.vcf.gz --out stdout --mean --vcftype eh"
+runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_popstr.sorted.vcf.gz --out stdout --mean --vcftype longtr"
 
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_advntr.sorted.vcf.gz --out stdout --mean --vcftype gangstr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_advntr.sorted.vcf.gz --out stdout --mean --vcftype hipstr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_advntr.sorted.vcf.gz --out stdout --mean --vcftype popstr"
 runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_advntr.sorted.vcf.gz --out stdout --mean --vcftype eh"
+runcmd_fail "statSTR --vcf ${EXDATADIR}/NA12878_chr21_advntr.sorted.vcf.gz --out stdout --mean --vcftype longtr"
+
 
 # Test mergeSTR on all supported tools
 # AdVNTR
@@ -191,6 +196,11 @@ FILE2=${EXDATADIR}/NA12891_chr21_popstr.sorted.vcf.gz
 FILE3=${EXDATADIR}/NA12892_chr21_popstr.sorted.vcf.gz
 runcmd_pass "mergeSTR --vcfs ${FILE1},${FILE2},${FILE3} --out ${TMPDIR}/test_merge_popstr --vcftype popstr"
 
+# LongTR
+FILE1=${EXDATADIR}/HG002_htt_test.vcf.gz
+FILE2=${EXDATADIR}/HG003_htt_test.vcf.gz
+runcmd_pass "mergeSTR --vcfs ${FILE1},${FILE2} --out ${TMPDIR}/test_merge_longtr --vcftype longtr"
+
 # Test mergeSTR on a file with list of VCFs
 FILE1=${EXDATADIR}/NA12878_chr21_hipstr.sorted.vcf.gz
 FILE2=${EXDATADIR}/NA12891_chr21_hipstr.sorted.vcf.gz
@@ -211,6 +221,7 @@ runcmd_pass "dumpSTR --vcf ${EXDATADIR}/NA12878_chr21_advntr.sorted.vcf.gz --adv
 runcmd_pass "dumpSTR --vcf ${EXDATADIR}/NA12878_chr21_eh.sorted.vcf.gz --out ${TMPDIR}/test_dumpstr_eh --eh-min-call-LC 50 --num-records 10 --drop-filtered"
 runcmd_pass "dumpSTR --vcf ${EXDATADIR}/trio_chr21_gangstr.sorted.vcf.gz --out ${TMPDIR}/test_dumpstr_gangstr --min-locus-callrate 0.9 --num-records 10"
 runcmd_pass "dumpSTR --vcf ${EXDATADIR}/trio_chr21_hipstr.sorted.vcf.gz --vcftype hipstr --out ${TMPDIR}/test_dumpstr_hipstr --filter-hrun --num-records 10"
+runcmd_pass "dumpSTR --vcf ${EXDATADIR}/longtr_testfile.vcf.gz --vcftype longtr --out ${TMPDIR}/test_dumpstr_longtr --use-length --filter-hrun --num-records 10"
 runcmd_pass "dumpSTR --vcf ${EXDATADIR}/trio_chr21_popstr.sorted.vcf.gz --out ${TMPDIR}/test_dumpstr_popstr --min-locus-callrate 0.9 --popstr-min-call-DP 10 --num-records 100"
 
 FILE1=${TMPDIR}/NA12878_advntr_reheader.vcf.gz
@@ -228,6 +239,7 @@ runcmd_pass "qcSTR --vcf ${EXDATADIR}/trio_chr21_hipstr.sorted.vcf.gz --out ${TM
 runcmd_pass "qcSTR --vcf ${EXDATADIR}/NA12878_chr21_eh.sorted.vcf.gz --out ${TMPDIR}/test_qc_eh"
 runcmd_pass "qcSTR --vcf ${EXDATADIR}/NA12878_chr21_advntr.sorted.vcf.gz --out ${TMPDIR}/test_qc_advntr"
 runcmd_pass "qcSTR --vcf ${EXDATADIR}/trio_chr21_popstr.sorted.vcf.gz --out ${TMPDIR}/test_qc_popstr"
+runcmd_pass "qcSTR --vcf ${EXDATADIR}/longtr_testfile.vcf.gz --vcftype longtr --out ${TMPDIR}/test_qc_longtr"
 
 runcmd_pass "qcSTR --vcf ${TMPDIR}/test_merge_gangstr.vcf --out ${TMPDIR}/test_qc_gangstr --period 4 --quality per-locus"
 runcmd_pass "qcSTR --vcf ${TMPDIR}/test_merge_hipstr.vcf --out ${TMPDIR}/test_qc_hipstr --vcftype hipstr --samples ${EXDATADIR}/ex-samples.txt"

trtools/annotaTR/README.rst

@@ -31,7 +31,7 @@ Required parameters:
 
 Other general parameters:
 
-* :code:`--vcftype <string>`: Which genotyping tool generated the input VCF. Default = :code:`auto`. Necessary if it cannot be automatically inferred. One of: :code:`gangstr`, :code:`advntr`, :code:`hipstr`, :code:`eh`, :code:`popstr`.
+* :code:`--vcftype <string>`: Which genotyping tool generated the input VCF. Default = :code:`auto`. Necessary if it cannot be automatically inferred. One of: :code:`gangstr`, :code:`advntr`, :code:`hipstr`, :code:`longtr`, :code:`eh`, :code:`popstr`.
 * :code:`--outtype <string>`: Which output format to generate. Supported output types are :code:`vcf` or :code:`pgen`. If multiple types are listed (e.g. :code:`--outtype vcf pgen`), all specified output formats are generated. By default, only VCF output is generated at :code:`$outprefix.vcf`. If PGEN output is specified, the files :code:`$outprefix.pgen`, :code:`$outprefix.pvar`, and :code:`$outprefix.psam` are generated. See more on the `pgen format here <https://www.cog-genomics.org/plink/2.0/formats#pgen>`_
 * :code:`--vcf-outtype <string>`: Type of VCF output to produce. This option is ignored unless using :code:`--outtype vcf`. Options: z=compressed VCF, v=uncompressed VCF, b=compressed BCF, u=uncompressed BCF, s=stdout
 * :code:`--region <str>`: Restrict to processing a specific genomic region. Syntax: chr:start-end.
@@ -111,7 +111,7 @@ Additional relevant options:
 
 If generating a VCF output file, this command will output a new file containing only STRs, with the following fields added back depending on the genotyper used to generate the reference panel:
 
-* For HipSTR-based reference panels: INFO fields START, END, PERIOD are added
+* For HipSTR-based or LongTR-based reference panels: INFO fields START, END, PERIOD are added
 * For adVNTR: INFO fields RU, VID are added
 * For GangSTR: INFO field RU is added
 * For ExpansionHunter: INFO fields RU, VARID, RL are added

trtools/annotaTR/annotaTR.py

@@ -25,6 +25,7 @@
 # Info fields copied from reference panel for each tool
 INFOFIELDS = {
     trh.VcfTypes.hipstr: ["START","END","PERIOD"],
+    trh.VcfTypes.longtr: ["START","END","PERIOD"],
     trh.VcfTypes.advntr: ["RU", "VID"],
     trh.VcfTypes.gangstr: ["RU"],
     trh.VcfTypes.eh: ["RU","VARID","RL"]

trtools/associaTR/README.rst

@@ -43,7 +43,7 @@ Required positional parameters:
 
 Optional input parameters:   
 
-* :code:`--vcftype` One of :code:`eh, hipstr, gangstr, popstr, advntr`
+* :code:`--vcftype` One of :code:`eh, hipstr, longtr, gangstr, popstr, advntr`
   Specify which caller produced the TR VCF, useful when the VCF is ambiguous 
   and the caller cannot be automatically inferred.
 * :code:`--same-samples` - see the description of traits above

trtools/associaTR/associaTR.py

@@ -17,6 +17,7 @@
 from . import load_and_filter_genotypes
 import trtools
 import trtools.utils.utils as utils
+import trtools.utils.tr_harmonizer as trh
 
 pval_precision = 2
 
@@ -491,7 +492,7 @@ def run():
         'Traits and the phenotype will be standardized to mean 0 and std 1 prior to regression, but '
         'coefficients/standard errors are transformed back to the original scale before being written out.'
     )
-    parser.add_argument('--vcftype', choices=['eh', 'hipstr', 'gangstr', 'popstr', 'advntr'],
+    parser.add_argument('--vcftype', choices=[str(item) for item in trh.VcfTypes.__members__],
                        help="Specify which caller produced the TR VCF, useful when the VCF is ambiguous "
                             "and the caller cannot be automatically inferred.")
     parser.add_argument('--same-samples', default=False, action='store_true',

trtools/dumpSTR/README.rst

@@ -29,7 +29,7 @@ See a description of output files below.
 Other general parameters:
 
 * :code:`--vcftype <string>`: Which genotyping tool generated the input VCF. Default = :code:`auto`.
-  Necessary if it cannot be automatically inferred. One of: :code:`gangstr`, :code:`advntr`, :code:`hipstr`, :code:`eh`, :code:`popstr`.
+  Necessary if it cannot be automatically inferred. One of: :code:`gangstr`, :code:`advntr`, :code:`hipstr`, :code:`longtr`, :code:`eh`, :code:`popstr`.
 * :code:`--zip` to output a bgzipped filtered VCF (:code:`$out.vcf.gz`) and tabix index (:code:`$out.vcf.gz.tbi`) instead of :code:`$out.vcf`.
 * :code:`--num-records <int>`: only process this many records from the input VCF file
 
@@ -60,10 +60,10 @@ These filters are not specific to any tool and can be applied to any VCF file:
 where p_i is the frequency of allele i
 
 * :code:`--max-locus-het <float>`: Filters loci with high heterozygosity
-* :code:`--use-length`: Use allele lengths, rather than sequences, to compute heterozygosity and HWE (only relevant for HipSTR, which reports sequence level differences in TR alleles)
+* :code:`--use-length`: Use allele lengths, rather than sequences, to compute heterozygosity and HWE (only relevant for HipSTR and LongTR, which report sequence level differences in TR alleles)
 * :code:`--filter-regions <BEDFILE[,BEDFILE12,...]>`: Filter TRs overlapping the specified set of regions. Must be used with :code:`--filter-regions-names`. Can supply a comma-separated list to each to apply multiple region filters. Bed files must be sorted and tabix-indexed. Note that regions are 0-based and inclusive of the start position, but exclusive of the end position.
 * :code:`--filter-regions-names <string[,string2,...]>`: Filter names for each BED file specified in :code:`--filter-regions`.
-* :code:`--filter-hrun`: Filter repeats with long homopolymer runs. Only used for HipSTR VCF files otherwise ignored. Filters pentanucleotides with homopolymer runs of 5bp or longer, or hexanucleotides with homopolymer runs of 6bp or longer.
+* :code:`--filter-hrun`: Filter repeats with long homopolymer runs. Only used for HipSTR or LongTR VCF files otherwise ignored. Filters pentanucleotides with homopolymer runs of 5bp or longer, or hexanucleotides with homopolymer runs of 6bp or longer.
 * :code:`--drop-filtered`: Do not output loci that were filtered, or loci with no calls remaining after filtering.
 
 TRs passing all locus-level filters will be marked as "PASS" in the FILTER field.
@@ -133,6 +133,14 @@ HipSTR call-level filters
 * :code:`--hipstr-max-call-DP <int>`: Maximum call coverage. Based on DP field.
 * :code:`--hipstr-min-call-Q <float>`: Minimum call quality score. Based on Q field.
 
+LongTR call-level filters
+**************************
+* :code:`--longtr-max-call-flank-indel <float>`: Maximum call flank indel rate. Computed as DFLANKINDEL/DP
+* :code:`--longtr-min-supp-reads <int>`: Minimum supporting reads for each allele. Based on ALLREADS and GB fields
+* :code:`--longtr-min-call-DP <int>`: Minimum call coverage. Based on DP field.
+* :code:`--longtr-max-call-DP <int>`: Maximum call coverage. Based on DP field.
+* :code:`--longtr-min-call-Q <float>`: Minimum call quality score. Based on Q field.
+
 PopSTR call-level filters
 **************************
 * :code:`--popstr-min-call-DP <int>`: Minimum call coverage. Based on DP field.
@@ -170,3 +178,6 @@ Below are :code:`dumpSTR` examples using VCFs from supported TR genotypers. Data
   # PopSTR
   dumpSTR --vcf trio_chr21_popstr.sorted.vcf.gz --out test_dumpstr_popstr --min-locus-callrate 0.9 --popstr-min-call-DP 10 --num-records 100
 
+  # LongTR
+  dumpSTR --vcf longtr_testfile.vcf.gz --vcftype longtr --out test_dumpstr_longtr --min-locus-callrate 0.9 --longtr-min-call-Q 0.9
+