PT  - JOURNAL ARTICLE
AU  - Sandeep Chakraborty
TI  - A plausible explanation for <em>in silico</em> reporting of erroneous MET gene expression in tumor-educated platelets (TEP) intended for “liquid biopsy” of non-small cell lung carcinoma still refutes the TEP-study
AID  - 10.1101/148718
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 148718
4099  - http://biorxiv.org/content/early/2017/06/11/148718.short
4100  - http://biorxiv.org/content/early/2017/06/11/148718.full
AB  - The reported over-expression of MET genes in non-small cell lung carcinoma (NSCLC) from an analysis of the RNA-seq data from tumor-educated platelets (TEP), intended to supplement existing ‘liquid biopsy’ techniques [1], has been refuted recently (http://biorxiv.org/content/early/2017/06/05/146134, not peer-reviewed). The MET proto-oncogene (Accid: NG 008996.1, RefSeqGene LRG_662 on chromosome 7, METwithintrons) encodes 21 exons resulting in a 6710 bps MET gene (Accid: NM_001127500.2, METonlyexons). METwithintrons has multiple matches in the RNA-seq derived reads of lung cancer samples (for example: SRR1982756.11853382). Unfortunately, these are non-specific sequences in the intronic regions, matching to multiple genes on different chromosomes with 100% identity (KIF6 on chr6, COL6A6 on chr3, MYO16 on chr13, etc. for SRR1982756.11853382). In contrast, METonlyexons has few matches in the reads, if at all [2]. However, even RNA-seq from healthy donors have similar matches for METwithintrons - so the computation behind the over-expression statistic remains obscure, even if METwithintrons was used as the search gene. In summary, this work re-iterates the lack of reproducibility in the bioinformatic analysis that establishes TEP as a possible source for “liquid biopsy”.