TMC-SNPdb 2.0

TMC-SNPdb 2.0 provides an ethnic-specific reference database of germline variants for the Indian population to improve somatic mutation identification in cancer genomics.

Key Features:

• Integration of Diverse Data Sources: Consolidates genome sequence data from GenomeAsia 100K (598 individuals) and Genomics for Public Health in India (IndiGen; 1,029 individuals) and incorporates unique variants from 173 normal germline samples collected from cancer patients at Tata Memorial Centre.
• Comprehensive Variant Collection: Contains 305,132 unique variants identified in the in-house samples, with 11.13% located in coding regions, missense variants comprising 31.3% of coding changes, and intronic variants accounting for 49% of non-coding variants.
• Utility in Somatic Variant Calling: Demonstrated reduction of false-positive somatic variant calls using GATK/Mutect2-based somatic variant calling on 224 tumor samples (paired and orphan), with an average depletion of 3.44% variants per paired tumor sample and 4.21% in orphan tumors.
• Enhanced Accuracy for Indian Populations: Provides a population-specific reference reflecting Indian genetic diversity to improve discrimination between inherited germline variants and somatic mutations in cancer analyses.

Scientific Applications:

• Somatic variant filtering: Reduces false-positive somatic calls in cancer genomics by using an Indian population-specific germline reference.
• Germline versus somatic distinction: Enables identification of inherited variants versus somatic mutations to support studies of cancer etiology and mutation interpretation in Indian cohorts.

Methodology:

Integrated variant data from GenomeAsia 100K, IndiGen, and 173 in-house normal germline samples and evaluated impact using GATK/Mutect2-based somatic variant calling on 224 tumor samples (paired and orphan).