The Wreaths of KHAN: Uniform Graph Feature Selection with False Discovery Rate Control

Fuente: arXiv
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Auteurs principaux: Liang, Jiajun, Liu, Yue, Zhou, Doudou, Zhang, Sinian, Lu, Junwei
Format: Preprint
Publié: 2024
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author Liang, Jiajun
Liu, Yue
Zhou, Doudou
Zhang, Sinian
Lu, Junwei
author_facet Liang, Jiajun
Liu, Yue
Zhou, Doudou
Zhang, Sinian
Lu, Junwei
contents Graphical models find numerous applications in biology, chemistry, sociology, neuroscience, etc. While substantial progress has been made in graph estimation, it remains largely unexplored how to select significant graph signals with uncertainty assessment, especially those graph features related to topological structures including cycles (i.e., wreaths), cliques, hubs, etc. These features play a vital role in protein substructure analysis, drug molecular design, and brain network connectivity analysis. To fill the gap, we propose a novel inferential framework for general high dimensional graphical models to select graph features with false discovery rate controlled. Our method is based on the maximum of $p$-values from single edges that comprise the topological feature of interest, thus is able to detect weak signals. Moreover, we introduce the $K$-dimensional persistent Homology Adaptive selectioN (KHAN) algorithm to select all the homological features within $K$ dimensions with the uniform control of the false discovery rate over continuous filtration levels. The KHAN method applies a novel discrete Gram-Schmidt algorithm to select statistically significant generators from the homology group. We apply the structural screening method to identify the important residues of the SARS-CoV-2 spike protein during the binding process to the ACE2 receptors. We score the residues for all domains in the spike protein by the $p$-value weighted filtration level in the network persistent homology for the closed, partially open, and open states and identify the residues crucial for protein conformational changes and thus being potential targets for inhibition.
format Preprint
id arxiv_https___arxiv_org_abs_2403_12284
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle The Wreaths of KHAN: Uniform Graph Feature Selection with False Discovery Rate Control
Liang, Jiajun
Liu, Yue
Zhou, Doudou
Zhang, Sinian
Lu, Junwei
Statistics Theory
Quantitative Methods
Applications
Methodology
Graphical models find numerous applications in biology, chemistry, sociology, neuroscience, etc. While substantial progress has been made in graph estimation, it remains largely unexplored how to select significant graph signals with uncertainty assessment, especially those graph features related to topological structures including cycles (i.e., wreaths), cliques, hubs, etc. These features play a vital role in protein substructure analysis, drug molecular design, and brain network connectivity analysis. To fill the gap, we propose a novel inferential framework for general high dimensional graphical models to select graph features with false discovery rate controlled. Our method is based on the maximum of $p$-values from single edges that comprise the topological feature of interest, thus is able to detect weak signals. Moreover, we introduce the $K$-dimensional persistent Homology Adaptive selectioN (KHAN) algorithm to select all the homological features within $K$ dimensions with the uniform control of the false discovery rate over continuous filtration levels. The KHAN method applies a novel discrete Gram-Schmidt algorithm to select statistically significant generators from the homology group. We apply the structural screening method to identify the important residues of the SARS-CoV-2 spike protein during the binding process to the ACE2 receptors. We score the residues for all domains in the spike protein by the $p$-value weighted filtration level in the network persistent homology for the closed, partially open, and open states and identify the residues crucial for protein conformational changes and thus being potential targets for inhibition.
title The Wreaths of KHAN: Uniform Graph Feature Selection with False Discovery Rate Control
topic Statistics Theory
Quantitative Methods
Applications
Methodology
url https://arxiv.org/abs/2403.12284