Detecting and overcoming systematic bias in high-throughput screening technologies: a comprehensive review of practical issues and methodological solutions

Briefings in Bioinformatics
Iurie CarausVladimir Makarenkov

Abstract

Significant efforts have been made recently to improve data throughput and data quality in screening technologies related to drug design. The modern pharmaceutical industry relies heavily on high-throughput screening (HTS) and high-content screening (HCS) technologies, which include small molecule, complementary DNA (cDNA) and RNA interference (RNAi) types of screening. Data generated by these screening technologies are subject to several environmental and procedural systematic biases, which introduce errors into the hit identification process. We first review systematic biases typical of HTS and HCS screens. We highlight that study design issues and the way in which data are generated are crucial for providing unbiased screening results. Considering various data sets, including the publicly available ChemBank data, we assess the rates of systematic bias in experimental HTS by using plate-specific and assay-specific error detection tests. We describe main data normalization and correction techniques and introduce a general data preprocessing protocol. This protocol can be recommended for academic and industrial researchers involved in the analysis of current or next-generation HTS data.

References

Dec 14, 2001·Biochemical and Biophysical Research Communications·K HonmaM Terada
Jan 9, 2004·Journal of Biomolecular Screening·Christine BrideauAndy Liaw
Apr 20, 2004·Assay and Drug Development Technologies·Kenneth A GiulianoD Lansing Taylor
Jan 13, 2005·Methods in Enzymology·Susan ArmknechtNorbert Perrimon
Aug 17, 2005·Journal of Biomolecular Screening·Dmytro Kevorkov, Vladimir Makarenkov
Oct 14, 2005·Journal of the American Chemical Society·Jeremiah S HelmSuzanne Walker
Jan 24, 2006·Journal of Chemical Information and Modeling·Andrew SmellieShi Chung Ng
Feb 9, 2006·Nature Biotechnology·Nathalie MaloRobert Nadon
Jul 28, 2006·Genome Biology·Michael BoutrosWolfgang Huber
Nov 10, 2006·Journal of Biomolecular Screening·Andrei GagarinPablo Zentilli
Apr 5, 2007·Molecular Pharmacology·John S LazoRay Dingledine
May 26, 2007·Current Opinion in Chemical Biology·Anang A Shelat, R Kiplin Guy
Jul 20, 2007·Nature Chemical Biology·James IngleseR Kiplin Guy
Sep 11, 2007·Nature Methods·Renate KönigSumit K Chanda
Sep 15, 2007·Nature Protocols·Nadire RamadanBernard Mathey-Prevot
Oct 13, 2007·Current Opinion in Chemical Biology·Kerstin Korn, Eberhard Krausz
May 16, 2008·Journal of Biomolecular Screening·Xiaohua Douglas ZhangMarc Ferrer
Jun 4, 2008·Nature Reviews. Genetics·Michael Boutros, Julie Ahringer
Jul 21, 2009·Nucleic Acids Research·Ricardo A VerdugoGary A Churchill
Jul 22, 2009·Nature Immunology·Sonia Sharma, Anjana Rao
Aug 1, 2009·Nature Methods·Amanda BirminghamCaroline E Shamu
Mar 17, 2010·Assay and Drug Development Technologies·Paul J BushwayMark Mercola
Mar 30, 2010·Trends in Biotechnology·Fabian ZanellaWolfgang Link
Apr 7, 2010·Annual Review of Biochemistry·Stephanie MohrNorbert Perrimon
May 5, 2010·Genetics·Paul L Auer, R W Doerge
Sep 8, 2010·Journal of Biomolecular Screening·Nathalie MaloRobert Nadon
Sep 15, 2010·Nature Reviews. Genetics·Jeffrey T LeekRafael A Irizarry
Oct 19, 2010·FEBS Letters·James A Koziol
Nov 16, 2010·Nature Methods·Anastasia BaryshnikovaChad L Myers
Jan 21, 2011·BMC Bioinformatics·Plamen DragievVladimir Makarenkov
Nov 29, 2011·Bioinformatics·Jean-Philippe CarralotThierry Dorval
May 9, 2012·Bioinformatics·Plamen DragievVladimir Makarenkov

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Citations

Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Samantha G PattendenIan J Davis
May 7, 2016·Bioinformatics·Alexander LachmannAndrea Califano
Feb 19, 2020·Expert Opinion on Drug Discovery·Joshua B HolmesJulian E Stelzer
Oct 30, 2016·Briefings in Bioinformatics·Shardul ParicharakGerard J P van Westen
Jun 24, 2018·Scientific Reports·Ivo D ShterevGregory D Sempowski
Jul 30, 2020·Pharmaceuticals·Sven Bulterijs, Bart P Braeckman
Jul 12, 2019·Frontiers in Oncology·Gabriela Klein CoutoTiago Collares
Oct 16, 2020·Scientific Reports·Samuel GoodwinQuentin S Hanley
Jan 29, 2021·The Plant Journal : for Cell and Molecular Biology·Ana Carolina A L CamposDavid E Salt
Mar 30, 2021·STAR Protocols·Stephan H SpangenbergLuke L Lairson
Aug 14, 2020·Journal of Chemical Information and Modeling·Natesh SinghBruno O Villoutreix
Mar 24, 2018·Molecular Pharmaceutics·Evgeny PutinAlex Zhavoronkov
Oct 23, 2021·Frontiers in Molecular Biosciences·M Kaan Arici, Nurcan Tuncbag
Mar 20, 2021··Reza Beheshti ZavarehStephan H. Spangenberg

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