JUMP: replicability analysis of high-throughput experiments with applications to spatial transcriptomic studies

被引:4
作者
Lyu, Pengfei [1 ]
Li, Yan [2 ]
Wen, Xiaoquan [3 ]
Cao, Hongyuan [1 ,2 ]
机构
[1] Florida State Univ, Dept Stat, 600 W Coll Ave, Tallahassee, FL 32306 USA
[2] Jilin Univ, Sch Math, 2699 Qianjin ST, Changchun 130012, Jilin, Peoples R China
[3] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
FALSE DISCOVERY RATE; GENE-EXPRESSION; REPRODUCIBILITY; IDENTIFICATION; REPLICATE; ATLAS;
D O I
10.1093/bioinformatics/btad366
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Motivation: Replicability is the cornerstone of scientific research. The current statistical method for high-dimensional replicability analysis either cannot control the false discovery rate (FDR) or is too conservative.Results: We propose a statistical method, JUMP, for the high-dimensional replicability analysis of two studies. The input is a high-dimensional paired sequence of p-values from two studies and the test statistic is the maximum of p-values of the pair. JUMP uses four states of the p-value pairs to indicate whether they are null or non-null. Conditional on the hidden states, JUMP computes the cumulative distribution function of the maximum of p-values for each state to conservatively approximate the probability of rejection under the composite null of replicability. JUMP estimates unknown parameters and uses a step-up procedure to control FDR. By incorporating different states of composite null, JUMP achieves a substantial power gain over existing methods while controlling the FDR. Analyzing two pairs of spatially resolved transcriptomic datasets, JUMP makes biological discoveries that otherwise cannot be obtained by using existing methods.
引用
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页数:8
相关论文
共 33 条
[1]  
Belluzzi O, 2003, J NEUROSCI, V23, P10411
[2]  
Benjamini Y, 2001, ANN STAT, V29, P1165
[3]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[4]   Selective inference in complex research [J].
Benjamini, Yoav ;
Heller, Ruth ;
Yekutieli, Daniel .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, 2009, 367 (1906) :4255-4271
[5]  
Bogomolov M, 2023, Arxiv, DOI arXiv:2210.00522
[6]   Assessing replicability of findings across two studies of multiple features [J].
Bogomolov, Marina ;
Heller, Ruth .
BIOMETRIKA, 2018, 105 (03) :505-516
[7]   Discovering Findings That Replicate From a Primary Study of High Dimension to a Follow-Up Study [J].
Bogomolov, Marina ;
Heller, Ruth .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 2013, 108 (504) :1480-1492
[8]   GPA: A Statistical Approach to Prioritizing GWAS Results by Integrating Pleiotropy and Annotation [J].
Chung, Dongjun ;
Yang, Can ;
Li, Cong ;
Gelernter, Joel ;
Zhao, Hongyu .
PLOS GENETICS, 2014, 10 (11)
[9]   Identification of spatial expression trends in single-cell gene expression data [J].
Edsgard, Daniel ;
Johnsson, Per ;
Sandberg, Rickard .
NATURE METHODS, 2018, 15 (05) :339-+
[10]  
Fisher R. A., 1946, Statistical methods for research workers.