PMID- 31143201
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231104
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 10
DP  - 2019
TI  - Quality Control of Quantitative High Throughput Screening Data.
PG  - 387
LID - 10.3389/fgene.2019.00387 [doi]
LID - 387
AB  - Quantitative high throughput screening (qHTS) experiments can generate 1000s of 
      concentration-response profiles to screen compounds for potentially adverse 
      effects. However, potency estimates for a single compound can vary considerably 
      in study designs incorporating multiple concentration-response profiles for each 
      compound. We introduce an automated quality control procedure based on analysis 
      of variance (ANOVA) to identify and filter out compounds with multiple cluster 
      response patterns and improve potency estimation in qHTS assays. Our approach, 
      called Cluster Analysis by Subgroups using ANOVA (CASANOVA), clusters 
      compound-specific response patterns into statistically supported subgroups. 
      Applying CASANOVA to 43 publicly available qHTS data sets, we found that only 
      about 20% of compounds with response values outside of the noise band have single 
      cluster responses. The error rates for incorrectly separating true clusters and 
      incorrectly clumping disparate clusters were both less than 5% in extensive 
      simulation studies. Simulation studies also showed that the bias and variance of 
      concentration at half-maximal response (AC(50) ) estimates were usually within 
      10-fold when using a weighted average approach for potency estimation. In short, 
      CASANOVA effectively sorts out compounds with "inconsistent" response patterns 
      and produces trustworthy AC(50) values.
FAU - Shockley, Keith R
AU  - Shockley KR
AD  - Biostatistics and Computational Biology Branch, National Institute of 
      Environmental Health Sciences, National Institutes of Health, Durham, NC, United 
      States.
FAU - Gupta, Shuva
AU  - Gupta S
AD  - Statistics Department, University of Pennsylvania, Philadelphia, PA, United 
      States.
FAU - Harris, Shawn F
AU  - Harris SF
AD  - Social and Scientific Systems, Durham, NC, United States.
FAU - Lahiri, Soumendra N
AU  - Lahiri SN
AD  - Department of Statistics, North Carolina State University, Raleigh, NC, United 
      States.
FAU - Peddada, Shyamal D
AU  - Peddada SD
AD  - Department of Biostatistics, Graduate School of Public Health, University of 
      Pittsburgh, Pittsburgh, PA, United States.
LA  - eng
GR  - HHSN273201600011C/ES/NIEHS NIH HHS/United States
GR  - ZIA ES102865/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20190509
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
PMC - PMC6520559
OTO - NOTNLM
OT  - ANOVA
OT  - clustering
OT  - concentration-response
OT  - potency
OT  - quantitative high throughput screening
OT  - toxicological response
EDAT- 2019/05/31 06:00
MHDA- 2019/05/31 06:01
PMCR- 2019/05/09
CRDT- 2019/05/31 06:00
PHST- 2018/05/24 00:00 [received]
PHST- 2019/04/10 00:00 [accepted]
PHST- 2019/05/31 06:00 [entrez]
PHST- 2019/05/31 06:00 [pubmed]
PHST- 2019/05/31 06:01 [medline]
PHST- 2019/05/09 00:00 [pmc-release]
AID - 10.3389/fgene.2019.00387 [doi]
PST - epublish
SO  - Front Genet. 2019 May 9;10:387. doi: 10.3389/fgene.2019.00387. eCollection 2019.