TDB: Tandem Repeat Database Queries

Tandem Repeats Team -- 2024 SVCC Hackathon

• Bishnu Adhikari
• Wouter De Coaster
• Adam English
• Emrah Kacar
• Rupesh Kesharwani
• Natali Gulbahce
• Moustafa Shokrof

Introduction

Our project’s ideas are around tdb. This tool turns ‘REPL’ style VCFs from tandem repeat callers into a database. This database compresses better than a VCF thanks to the parquet format and has better structured data that is easier to parse than VCFs. There are currently a handful of ‘standard’ queries and analysis notebooks which can provide useful summaries of tandem repeat results. For the hackathon, we can make some new, interesting queries.

Data

HPRC 105 TDB made as part of the Human Pangenome Reference Consortium (HPRC) which represents a subset of HPRC and presents genomic diversity across 105 indivuduals (https://www.nature.com/articles/s41587-023-02057-3).

• Total Samples: 105
• Total TR loci: 937,122
• Total TR span: 121,698,022 bp (4% of grch38)
• TR catalog: Adotto v0.3

Population	Count
AFR	52
AMR	56
EAS	32
SAS	48
UNK	8

Result #1 - GTF annotation

The script Emrah_EDA/tdb_gtf_anno.py will annotate the TR loci with gene information in a gtf such as this from gencode.

Example Usage

python tdb_gtf_anno.py \
    hprc_105.tdb \
    gencode.v38.annotation.gtf.gz > output.txt

You can optionally subset to specific loci with --locusids or tdb chromosomes with --chrom.

Example output:

LocusID	hits_gene	hits_exon	gene_name
132443	True	False	KIAA1549L
271491	False	False
347074	True	False	CCDC200
347381	False	False
385018	True	False	GTSCR1
396168	True	False	ZNF433-AS1,CTC-359D24.6
453703	True	True	TMEM87B
520559	False	False
585194	True	False	PIK3CB

Result #2 - Population Statistics

Allele Counts

To annotate made the allele counts English_EDA/population_ac_by_length.py

Usage:

python population_ac_by_length.py \
    hprc_105.tdb metadata.tsv -o result.txt

Example output:

chrom	start	end	is_ref	AC	AF	AC_EAS	AC_AMR	AC_AFR	AC_SAS	AC_UNK
chr1	72059	72194	True	145	0.7474226804123711	15	24	22	19	8
chr1	72059	72194	False	11	0.05670103092783505	1	0	1	8	0

Length polymorphism

The length polymorphism score is a per-locus measure of the proportion of distinct alleles by length over the total alleles measured at a locus

Usage:

tdb query len_poly_score hprc_105.tdb > result.txt

Example output:

chrom	start	end	len_poly_score
chr1	16682	16774	1.9047619047619047
chr1	19275	19473	1.9047619047619047
chr1	20798	20893	1.9047619047619047

Fst

Fixation index (Fst) is a measure of genetic differentiation between populations, quantifying the proportion of genetic variance due to population structure. Here we calculated Fst of TR alleles across loci, we first run a query to calculate allele counts by population using population_ac_by_length.py to create input_allele_counts.tsv. We use an equation from Joshua Sampson et al. (2012).

Usage:

python calculate_fst.py -o result.tsv input_allele_counts.tsv 

Example output:

 chrom   start   end     is_ref  AC      AF      AC_EAS  AC_AMR  AC_AFR  AC_SAS  fst     fst_SAS_EAS     fst_SAS_AMR     fst_SAS_AFR     fst_EAS_AMR      fst_EAS_AFR     fst_AMR_AFR
0       chr1    16682   16774   True    161     0.8563829787234043      16      28      26      24      0.0032071247201271857   0.0     0.00073260073260073      0.004571428571428449    0.0006734006734007147   0.004186289900575568    0.0016737559221220444
1       chr1    16682   16774   False   27      0.1436170212765957      4       8       9       6       0.0032071247201269637   0.0     0.00073260073260073      0.004571428571428449    0.0006734006734007147   0.004186289900575457    0.0016737559221218223
2       chr1    19275   19473   True    178     0.946808510638298       16      28      26      24      0.0770754352030949      0.015999999999999903    0.0034188034188034067    0.061103030303030215    0.024242424242424176    0.08080808080808077     0.0430976430976433

Result #3 - Population Informative TR Loci

See this notebook for details.