title: Comprehensive analysis of high-throughput screens with HiTSeekR.
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.
authors.affiliation: 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 markus.list@mpi-inf.mpg.de.
authors.forename: Markus
authors.identifier: 0000-0002-0941-4168
authors.initials: M
authors.lastname: List
authors.affiliation: 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.
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: 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.
authors.forename: Helle
authors.initials: H
authors.lastname: Christiansen
authors.affiliation: Computational Biology Unit, Department of Informatics, University of Bergen, 5020 Bergen, Norway.
authors.forename: Marc
authors.initials: M
authors.lastname: Rehmsmeier
authors.affiliation: Clinical Institute (CI), University of Southern Denmark, 5000 Odense, Denmark Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, 5000 Odense, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Jan
authors.initials: J
authors.lastname: Mollenhauer
authors.affiliation: Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, 5230 Odense, Denmark Max Planck Institute for Informatics, 66123 Saarbrücken, Germany jbaumbac@mpi-inf.mpg.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Baumbach
mesh_terms: D020169:Caspases / Q000378:metabolism; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011786:Quality Control; D034622:RNA Interference; D012371:Robotics; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases