Pair Matcher (PaM): Fast Model-based Optimization of Treatment/case-control Matches

Overview

Journal Bioinformatics

Publisher Oxford University Press

Specialty Biology

Date 2018 Nov 17

PMID 30445488

Citations 6

Authors

Eran Elhaik

Desmond M Ryan

Affiliations

Soon will be listed here.

Abstract

Motivation: In clinical trials, individuals are matched using demographic criteria, paired and then randomly assigned to treatment and control groups to determine a drug's efficacy. A chief cause for the irreproducibility of results across pilot to Phase-III trials is population stratification bias caused by the uneven distribution of ancestries in the treatment and control groups.

Results: Pair Matcher (PaM) addresses stratification bias by optimizing pairing assignments a priori and/or a posteriori to the trial using both genetic and demographic criteria. Using simulated and real datasets, we show that PaM identifies ideal and near-ideal pairs that are more genetically homogeneous than those identified based on competing methods, including the commonly used principal component analysis (PCA). Homogenizing the treatment (or case) and control groups can be expected to improve the accuracy and reproducibility of the trial or genetic study. PaM's ancestral inferences also allow characterizing responders and developing a precision medicine approach to treatment.

Availability And Implementation: PaM is freely available via Rhttps://github.com/eelhaik/PAM and a web-interface at http://elhaik-matcher.sheffield.ac.uk/ElhaikLab/.

Supplementary Information: Supplementary data are available at Bioinformatics online.

Citing Articles

Temporal population structure, a genetic dating method for ancient Eurasian genomes from the past 10,000 years.

Behnamian S, Esposito U, Holland G, Alshehab G, Dobre A, Pirooznia M Cell Rep Methods. 2022; 2(8):100270.

PMID: 36046618 PMC: 9421539. DOI: 10.1016/j.crmeth.2022.100270.

Principal Component Analyses (PCA)-based findings in population genetic studies are highly biased and must be reevaluated.

Elhaik E Sci Rep. 2022; 12(1):14683.

PMID: 36038559 PMC: 9424212. DOI: 10.1038/s41598-022-14395-4.

Systems biology analysis of human genomes points to key pathways conferring spina bifida risk.

Aguiar-Pulido V, Wolujewicz P, Martinez-Fundichely A, Elhaik E, Thareja G, Abdel Aleem A Proc Natl Acad Sci U S A. 2021; 118(51).

PMID: 34916285 PMC: 8713748. DOI: 10.1073/pnas.2106844118.

Unraveling the complex genetics of neural tube defects: From biological models to human genomics and back.

Wolujewicz P, Steele J, Kaltschmidt J, Finnell R, Ross M Genesis. 2021; 59(11):e23459.

PMID: 34713546 PMC: 8851409. DOI: 10.1002/dvg.23459.

Population genetic considerations for using biobanks as international resources in the pandemic era and beyond.

Carress H, Lawson D, Elhaik E BMC Genomics. 2021; 22(1):351.

PMID: 34001009 PMC: 8127217. DOI: 10.1186/s12864-021-07618-x.

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