A U-statistics for Integrative Analysis of Multilayer Omics Data

Overview

Journal Bioinformatics

Publisher Oxford University Press

Specialty Biology

Date 2020 Jan 9

PMID 31913435

Citations 1

Authors

Xiaqiong Wang

Yalu Wen

Affiliations

Soon will be listed here.

Abstract

Motivation: The emerging multilayer omics data provide unprecedented opportunities for detecting biomarkers that are associated with complex diseases at various molecular levels. However, the high-dimensionality of multiomics data and the complex disease etiologies have brought tremendous analytical challenges.

Results: We developed a U-statistics-based non-parametric framework for the association analysis of multilayer omics data, where consensus and permutation-based weighting schemes are developed to account for various types of disease models. Our proposed method is flexible for analyzing different types of outcomes as it makes no assumptions about their distributions. Moreover, it explicitly accounts for various types of underlying disease models through weighting schemes and thus provides robust performance against them. Through extensive simulations and the application to dataset obtained from the Alzheimer's Disease Neuroimaging Initiatives, we demonstrated that our method outperformed the commonly used kernel regression-based methods.

Availability And Implementation: The R-package is available at https://github.com/YaluWen/Uomic.

Supplementary Information: Supplementary data are available at Bioinformatics online.

Citing Articles

The systematic comparison between Gaussian mirror and Model-X knockoff models.

Chen S, Li Z, Liu L, Wen Y Sci Rep. 2023; 13(1):5478.

PMID: 37015993 PMC: 10073103. DOI: 10.1038/s41598-023-32605-5.

References

Johnson S, La Rue A, Hermann B, Xu G, Koscik R, Jonaitis E . The effect of TOMM40 poly-T length on gray matter volume and cognition in middle-aged persons with APOE ε3/ε3 genotype. Alzheimers Dement. 2011; 7(4):456-65. PMC: 3143375. DOI: 10.1016/j.jalz.2010.11.012. View

Christensen H, Batterham P, Mackinnon A, Jorm A, Mack H, Mather K . The association of APOE genotype and cognitive decline in interaction with risk factors in a 65-69 year old community sample. BMC Geriatr. 2008; 8:14. PMC: 2488328. DOI: 10.1186/1471-2318-8-14. View

Zeng I, Lumley T . Review of Statistical Learning Methods in Integrated Omics Studies (An Integrated Information Science). Bioinform Biol Insights. 2018; 12:1177932218759292. PMC: 5824897. DOI: 10.1177/1177932218759292. View

Wu C, Ma S . A selective review of robust variable selection with applications in bioinformatics. Brief Bioinform. 2014; 16(5):873-83. PMC: 4570200. DOI: 10.1093/bib/bbu046. View

Phan J, Quo C, Cheng C, Wang M . Multiscale integration of -omic, imaging, and clinical data in biomedical informatics. IEEE Rev Biomed Eng. 2012; 5:74-87. PMC: 5859561. DOI: 10.1109/RBME.2012.2212427. View

Ni H, Xu M, Zhan G, Fan Y, Zhou H, Jiang H . The GWAS Risk Genes for Depression May Be Actively Involved in Alzheimer's Disease. J Alzheimers Dis. 2018; 64(4):1149-1161. DOI: 10.3233/JAD-180276. View

Yan Q, Liu N, Forno E, Canino G, Celedon J, Chen W . An integrative association method for omics data based on a modified Fisher's method with application to childhood asthma. PLoS Genet. 2019; 15(5):e1008142. PMC: 6524814. DOI: 10.1371/journal.pgen.1008142. View

Chiba-Falek O, Gottschalk W, Lutz M . The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes. Alzheimers Dement. 2018; 14(5):692-698. PMC: 5938113. DOI: 10.1016/j.jalz.2018.01.015. View

Santarelli S, Namendorf C, Anderzhanova E, Gerlach T, Bedenk B, Kaltwasser S . The amino acid transporter SLC6A15 is a regulator of hippocampal neurochemistry and behavior. J Psychiatr Res. 2015; 68:261-9. DOI: 10.1016/j.jpsychires.2015.07.012. View

10.

Roberts R, Kang Y, Hu C, Moser C, Wang S, Moore M . Decreased Expression of Sulfatase 2 in the Brains of Alzheimer's Disease Patients: Implications for Regulation of Neuronal Cell Signaling. J Alzheimers Dis Rep. 2018; 1(1):115-124. PMC: 6052874. DOI: 10.3233/ADR-170028. View

11.

Mariette J, Villa-Vialaneix N . Unsupervised multiple kernel learning for heterogeneous data integration. Bioinformatics. 2017; 34(6):1009-1015. DOI: 10.1093/bioinformatics/btx682. View

12.

Huang Y . Integrative modeling of multiple genomic data from different types of genetic association studies. Biostatistics. 2014; 15(4):587-602. DOI: 10.1093/biostatistics/kxu014. View

13.

Choi S, Han K, Kang J, Won E, Chang H, Tae W . Effects of a Polymorphism of the Neuronal Amino Acid Transporter SLC6A15 Gene on Structural Integrity of White Matter Tracts in Major Depressive Disorder. PLoS One. 2016; 11(10):e0164301. PMC: 5056691. DOI: 10.1371/journal.pone.0164301. View

14.

Liu S, Liu Y, Hao W, Wolf L, Kiliaan A, Penke B . TLR2 is a primary receptor for Alzheimer's amyloid β peptide to trigger neuroinflammatory activation. J Immunol. 2011; 188(3):1098-107. DOI: 10.4049/jimmunol.1101121. View

15.

Zhou Q, Zhao F, Lv Z, Zheng C, Zheng W, Sun L . Association between APOC1 polymorphism and Alzheimer's disease: a case-control study and meta-analysis. PLoS One. 2014; 9(1):e87017. PMC: 3909044. DOI: 10.1371/journal.pone.0087017. View

16.

Su Z, Marchini J, Donnelly P . HAPGEN2: simulation of multiple disease SNPs. Bioinformatics. 2011; 27(16):2304-5. PMC: 3150040. DOI: 10.1093/bioinformatics/btr341. View

17.

Hoffmann K, Sobol N, Frederiksen K, Beyer N, Vogel A, Vestergaard K . Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer's Disease: A Randomized Controlled Trial. J Alzheimers Dis. 2015; 50(2):443-53. DOI: 10.3233/JAD-150817. View

18.

Wu C, Zhou F, Ren J, Li X, Jiang Y, Ma S . A Selective Review of Multi-Level Omics Data Integration Using Variable Selection. High Throughput. 2019; 8(1). PMC: 6473252. DOI: 10.3390/ht8010004. View

19.

Ertekin-Taner N . Genetics of Alzheimer's disease: a centennial review. Neurol Clin. 2007; 25(3):611-67, v. PMC: 2735049. DOI: 10.1016/j.ncl.2007.03.009. View

20.

Corder E, Saunders A, Strittmatter W, Schmechel D, Gaskell P, Small G . Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993; 261(5123):921-3. DOI: 10.1126/science.8346443. View