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Focused goodness of fit tests for gene set analyses.

Publication ,  Journal Article
Zhang, M; Gelfman, S; Martins Moreno, CA; McCarthy, JM; Harms, MB; Goldstein, DB; Allen, AS
Published in: Brief Bioinform
January 17, 2022

Gene set-based signal detection analyses are used to detect an association between a trait and a set of genes by accumulating signals across the genes in the gene set. Since signal detection is concerned with identifying whether any of the genes in the gene set are non-null, a goodness-of-fit (GOF) test can be used to compare whether the observed distribution of gene-level tests within the gene set agrees with the theoretical null distribution. Here, we present a flexible gene set-based signal detection framework based on tail-focused GOF statistics. We show that the power of the various statistics in this framework depends critically on two parameters: the proportion of genes within the gene set that are non-null and the degree of separation between the null and alternative distributions of the gene-level tests. We give guidance on which statistic to choose for a given situation and implement the methods in a fast and user-friendly R package, wHC (https://github.com/mqzhanglab/wHC). Finally, we apply these methods to a whole exome sequencing study of amyotrophic lateral sclerosis.

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Published In

Brief Bioinform

DOI

EISSN

1477-4054

Publication Date

January 17, 2022

Volume

23

Issue

1

Location

England

Related Subject Headings

  • Phenotype
  • Humans
  • Genetic Testing
  • Exome Sequencing
  • Bioinformatics
  • Amyotrophic Lateral Sclerosis
  • 3105 Genetics
  • 3102 Bioinformatics and computational biology
  • 3101 Biochemistry and cell biology
  • 0899 Other Information and Computing Sciences
 

Citation

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Zhang, M., Gelfman, S., Martins Moreno, C. A., McCarthy, J. M., Harms, M. B., Goldstein, D. B., & Allen, A. S. (2022). Focused goodness of fit tests for gene set analyses. Brief Bioinform, 23(1). https://doi.org/10.1093/bib/bbab472
Zhang, Mengqi, Sahar Gelfman, Cristiane Araujo Martins Moreno, Janice M. McCarthy, Matthew B. Harms, David B. Goldstein, and Andrew S. Allen. “Focused goodness of fit tests for gene set analyses.Brief Bioinform 23, no. 1 (January 17, 2022). https://doi.org/10.1093/bib/bbab472.
Zhang M, Gelfman S, Martins Moreno CA, McCarthy JM, Harms MB, Goldstein DB, et al. Focused goodness of fit tests for gene set analyses. Brief Bioinform. 2022 Jan 17;23(1).
Zhang, Mengqi, et al. “Focused goodness of fit tests for gene set analyses.Brief Bioinform, vol. 23, no. 1, Jan. 2022. Pubmed, doi:10.1093/bib/bbab472.
Zhang M, Gelfman S, Martins Moreno CA, McCarthy JM, Harms MB, Goldstein DB, Allen AS. Focused goodness of fit tests for gene set analyses. Brief Bioinform. 2022 Jan 17;23(1).
Journal cover image

Published In

Brief Bioinform

DOI

EISSN

1477-4054

Publication Date

January 17, 2022

Volume

23

Issue

1

Location

England

Related Subject Headings

  • Phenotype
  • Humans
  • Genetic Testing
  • Exome Sequencing
  • Bioinformatics
  • Amyotrophic Lateral Sclerosis
  • 3105 Genetics
  • 3102 Bioinformatics and computational biology
  • 3101 Biochemistry and cell biology
  • 0899 Other Information and Computing Sciences