List Markus, Schmidt Steffen, Christiansen Helle, Rehmsmeier Marc, Tan Qihua, Mollenhauer Jan, Baumbach Jan
Lundbeckfonden Center of Excellence in Nanomedicine (NanoCAN), University of Southern Denmark, 5000 Odense, Denmark Molecular Oncology, Institute of Molecular Medicin (IMM), University of Southern Denmark, 5000 Odense, Denmark Clinical Institute (CI), University of Southern Denmark, 5000 Odense, Denmark
Lundbeckfonden Center of Excellence in Nanomedicine (NanoCAN), University of Southern Denmark, 5000 Odense, Denmark Molecular Oncology, Institute of Molecular Medicin (IMM), University of Southern Denmark, 5000 Odense, Denmark.
Nucleic Acids Res. 2016 Aug 19;44(14):6639-48. doi: 10.1093/nar/gkw554. Epub 2016 Jun 21.
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.
高通量筛选（HTS）是药物（靶点）发现中不可或缺的工具，目前缺乏用户友好的软件工具，无法从HTS实验中可靠地识别潜在命中物，并在系统生物学背景下解释这些发现。我们开发了HiTSeekR，作为化合物筛选、siRNA敲低和CRISPR/Cas9敲除筛选以及microRNA抑制剂和模拟物筛选的一站式解决方案。我们选择了三个用例，展示了HiTSeekR在完全不同的背景下充分利用HTS筛选数据以生成后续实验新假设的潜力：（i）全基因组RNAi筛选以发现TNFα调节剂，（ii）关于伏立诺他耐药性的siRNA和miRNA模拟物联合筛选，以及（iii）关于KRAS合成致死性的小分子化合物筛选。HiTSeekR可在http://hitseekr.compbio.sdu.dk上公开获取。它是第一种弥合各种HTS筛选类型的原始数据处理、网络富集和湿实验室靶点生成之间差距的方法。
