Comparability of mixed IC₅₀ data - a statistical analysis.

The biochemical half maximal inhibitory concentration (IC50) is the most commonly used metric for on-target activity in lead optimization. It is used to guide lead optimization, build large-scale chemogenomics analysis, off-target activity and toxicity models based on public data. However, the use o...

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Autores principales:	Tuomo Kalliokoski, Christian Kramer, Anna Vulpetti, Peter Gedeck
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b8bfc43bccf466eabd6521aa7fa7320
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spelling	oai:doaj.org-article:8b8bfc43bccf466eabd6521aa7fa73202021-11-18T07:49:23ZComparability of mixed IC₅₀ data - a statistical analysis.1932-620310.1371/journal.pone.0061007https://doaj.org/article/8b8bfc43bccf466eabd6521aa7fa73202013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23613770/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The biochemical half maximal inhibitory concentration (IC50) is the most commonly used metric for on-target activity in lead optimization. It is used to guide lead optimization, build large-scale chemogenomics analysis, off-target activity and toxicity models based on public data. However, the use of public biochemical IC50 data is problematic, because they are assay specific and comparable only under certain conditions. For large scale analysis it is not feasible to check each data entry manually and it is very tempting to mix all available IC50 values from public database even if assay information is not reported. As previously reported for Ki database analysis, we first analyzed the types of errors, the redundancy and the variability that can be found in ChEMBL IC50 database. For assessing the variability of IC50 data independently measured in two different labs at least ten IC50 data for identical protein-ligand systems against the same target were searched in ChEMBL. As a not sufficient number of cases of this type are available, the variability of IC50 data was assessed by comparing all pairs of independent IC50 measurements on identical protein-ligand systems. The standard deviation of IC50 data is only 25% larger than the standard deviation of Ki data, suggesting that mixing IC50 data from different assays, even not knowing assay conditions details, only adds a moderate amount of noise to the overall data. The standard deviation of public ChEMBL IC50 data, as expected, resulted greater than the standard deviation of in-house intra-laboratory/inter-day IC50 data. Augmenting mixed public IC50 data by public Ki data does not deteriorate the quality of the mixed IC50 data, if the Ki is corrected by an offset. For a broad dataset such as ChEMBL database a Ki- IC50 conversion factor of 2 was found to be the most reasonable.Tuomo KalliokoskiChristian KramerAnna VulpettiPeter GedeckPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61007 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tuomo Kalliokoski Christian Kramer Anna Vulpetti Peter Gedeck Comparability of mixed IC₅₀ data - a statistical analysis.
description	The biochemical half maximal inhibitory concentration (IC50) is the most commonly used metric for on-target activity in lead optimization. It is used to guide lead optimization, build large-scale chemogenomics analysis, off-target activity and toxicity models based on public data. However, the use of public biochemical IC50 data is problematic, because they are assay specific and comparable only under certain conditions. For large scale analysis it is not feasible to check each data entry manually and it is very tempting to mix all available IC50 values from public database even if assay information is not reported. As previously reported for Ki database analysis, we first analyzed the types of errors, the redundancy and the variability that can be found in ChEMBL IC50 database. For assessing the variability of IC50 data independently measured in two different labs at least ten IC50 data for identical protein-ligand systems against the same target were searched in ChEMBL. As a not sufficient number of cases of this type are available, the variability of IC50 data was assessed by comparing all pairs of independent IC50 measurements on identical protein-ligand systems. The standard deviation of IC50 data is only 25% larger than the standard deviation of Ki data, suggesting that mixing IC50 data from different assays, even not knowing assay conditions details, only adds a moderate amount of noise to the overall data. The standard deviation of public ChEMBL IC50 data, as expected, resulted greater than the standard deviation of in-house intra-laboratory/inter-day IC50 data. Augmenting mixed public IC50 data by public Ki data does not deteriorate the quality of the mixed IC50 data, if the Ki is corrected by an offset. For a broad dataset such as ChEMBL database a Ki- IC50 conversion factor of 2 was found to be the most reasonable.
format	article
author	Tuomo Kalliokoski Christian Kramer Anna Vulpetti Peter Gedeck
author_facet	Tuomo Kalliokoski Christian Kramer Anna Vulpetti Peter Gedeck
author_sort	Tuomo Kalliokoski
title	Comparability of mixed IC₅₀ data - a statistical analysis.
title_short	Comparability of mixed IC₅₀ data - a statistical analysis.
title_full	Comparability of mixed IC₅₀ data - a statistical analysis.
title_fullStr	Comparability of mixed IC₅₀ data - a statistical analysis.
title_full_unstemmed	Comparability of mixed IC₅₀ data - a statistical analysis.
title_sort	comparability of mixed ic₅₀ data - a statistical analysis.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8b8bfc43bccf466eabd6521aa7fa7320
work_keys_str_mv	AT tuomokalliokoski comparabilityofmixedic50dataastatisticalanalysis AT christiankramer comparabilityofmixedic50dataastatisticalanalysis AT annavulpetti comparabilityofmixedic50dataastatisticalanalysis AT petergedeck comparabilityofmixedic50dataastatisticalanalysis
_version_	1718422923936530432

Comparability of mixed IC₅₀ data - a statistical analysis.

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