Comprehensive analysis of high-throughput screens with HiTSeekR

Nucleic Acids Res. 2016 Aug 19;44(14):6639-48. doi: 10.1093/nar/gkw554. Epub 2016 Jun 21.

Abstract

High-throughput screening (HTS) is an indispensable tool for drug (target) discovery that currently lacks user-friendly software tools for the robust identification of putative hits from HTS experiments and for the interpretation of these findings in the context of systems biology. We developed HiTSeekR as a one-stop solution for chemical compound screens, siRNA knock-down and CRISPR/Cas9 knock-out screens, as well as microRNA inhibitor and -mimics screens. We chose three use cases that demonstrate the potential of HiTSeekR to fully exploit HTS screening data in quite heterogeneous contexts to generate novel hypotheses for follow-up experiments: (i) a genome-wide RNAi screen to uncover modulators of TNFα, (ii) a combined siRNA and miRNA mimics screen on vorinostat resistance and (iii) a small compound screen on KRAS synthetic lethality. HiTSeekR is publicly available at http://hitseekr.compbio.sdu.dk It is the first approach to close the gap between raw data processing, network enrichment and wet lab target generation for various HTS screen types.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspases / metabolism
  • Drug Delivery Systems
  • Drug Evaluation, Preclinical*
  • High-Throughput Screening Assays / methods*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Quality Control
  • RNA Interference
  • Robotics
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Caspases