title: Using high-throughput sequencing transcriptome data for INDEL detection: challenges for cancer drug discovery.
abstract: BACKGROUND
  A cancer cell is a mosaic of genomic and epigenomic alterations. Distinct cancer molecular signatures can be observed depending on tumor type or patient genetic background. One type of genomic alteration is the insertion and/or deletion (INDEL) of nucleotides in the DNA sequence, which may vary in length, and may change the encoded protein or modify protein domains. INDELs are associated to a large number of diseases and their detection is done based on low-throughput techniques. However, high-throughput sequencing has also started to be used for detection of novel disease-causing INDELs. This search may identify novel drug targets.
  
  
  METHODS
  This review presents examples of using high-throughput sequencing (DNA-Seq and RNA-Seq) to investigate the incidence of INDELs in coding regions of human genes. Some of these examples successfully utilized RNA-Seq to identify INDELs associated to diseases. In addition, other studies have described small INDELs related to chemo-resistance or poor outcome of patients, while structural variants were associated with a better clinical outcome.
  
  
  CONCLUSIONS
  On average, there is twice as much RNA-Seq data available at the most used repositories for such data compared to DNA-Seq. Therefore, using RNA-Seq data is a promising strategy for studying cancer samples with unknown mechanisms of drug resistance, aiming at the discovery of proteins with potential as novel drug targets.
authors.affiliation: a Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute , Fundação Oswaldo Cruz (FIOCRUZ) , Rio de Janeiro , RJ , Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Wajnberg
authors.affiliation: a Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute , Fundação Oswaldo Cruz (FIOCRUZ) , Rio de Janeiro , RJ , Brazil.
authors.forename: Fabio
authors.initials: F
authors.lastname: Passetti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods*; D019008:Drug Resistance, Neoplasm; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D054643:INDEL Mutation; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods; D017423:Sequence Analysis, RNA / Q000379:methods; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents
keywords: Bioinformatics; INDEL; RNA-Seq; drug; transcriptomics