finding mutations in RNA-Seq data

Question

[Abhi]

Hey Guys

Just wondering if someone can point me to any literature for finding mutations in the RNA-Seq data. Google did take me to few interesting blogs but not sure if I covered the recommended methods out there.

Cheers!

-Abhi

Answer 1

[Charles Warden]

GATK has "best practices" for calling variants in RNA-Seq:

http://gatkforums.broadinstitute.org/discussion/3891/calling-variants-in-rnaseq

That said, the interpretation is not trivial: without paired DNA-Seq data, it may not be safe to assume the mutation first occurred at the DNA level, both alleles are being expressed, etc.

Answer 2

[Ashutosh Pandey]

You may find this paper helpful.

Reliable Identification of Genomic Variants from RNA-Seq Data

Identifying genomic variation is a crucial step for unraveling the relationship between genotype and phenotype and can yield important insights into human diseases. Prevailing methods rely on cost-intensive whole-genome sequencing (WGS) or whole-exome sequencing (WES) approaches while the identification of genomic variants from often existing RNA sequencing (RNA-seq) data remains a challenge because of the intrinsic complexity in the transcriptome. Here, we present a highly accurate approach termed SNPiR to identify SNPs in RNA-seq data. We applied SNPiR to RNA-seq data of samples for which WGS and WES data are also available and achieved high specificity and sensitivity. Of the SNPs called from the RNA-seq data, >98% were also identified by WGS or WES. Over 70% of all expressed coding variants were identified from RNA-seq, and comparable numbers of exonic variants were identified in RNA-seq and WES. Despite our method's limitation in detecting variants in expressed regions only, our results demonstrate that SNPiR outperforms current state-of-the-art approaches for variant detection from RNA-seq data and offers a cost-effective and reliable alternative for SNP discovery.