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rPCMP: robust p-value combination by multiple partitions with applications to ATAC-seq data.

Menglan Cai1, Limin Li2

  • 1School of Mathematics and Statistics, Xi'an Jiaotong University, Xianning West 28, Xi'an, China.

BMC Systems Biology
|January 2, 2019
PubMed
Summary

We developed a robust p-value combination method (rPCMP) to improve statistical power for analyzing gene significance in diseases. Our method enhances cancer treatment strategy by identifying key pathways and gene functions.

Keywords:
ATAC-seqgroup p-valuemultiple partitions

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Area of Science:

  • Genomics
  • Bioinformatics
  • Cancer Research

Background:

  • Understanding gene/protein significance in disease pathways is crucial for elucidating disease mechanisms.
  • Identifying pathways and gene functions related to tumor-specific T cell chromatin states aids in determining T cell reprograming potential and cancer treatment strategies.

Purpose of the Study:

  • To develop a more powerful and robust statistical method for combining p-values, addressing limitations of existing approaches.
  • To improve the analysis of gene set enrichment and pathway significance in complex diseases.

Main Methods:

  • Proposed a robust p-value combination method (rPCMP) with a three-layer hierarchical structure.
  • rPCMP considers multiple partitions of p-values using different truncation points.
  • Empirical null distribution is estimated via permutation procedures.

Main Results:

  • The rPCMP method demonstrates increased robustness and statistical power compared to existing methods.
  • Simulation studies confirm effective control of type I error rates and superior power.
  • The method was successfully applied to an ATAC-seq dataset for mouse tumor T cells.

Conclusions:

  • The proposed rPCMP method offers a significant advancement in statistical power and robustness for p-value combination.
  • rPCMP facilitates the discovery of biologically relevant gene functions and pathways.
  • This method can aid in developing more effective cancer treatment strategies.