Variance-Preserving Estimation of Intensity Values Obtained From Omics Experiments

Autor(es)

Ribeiro, Adele H. ^[1] ; Pavan Soler, Julia Maria ^[2] ; Hirata Jr, Roberto

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Comp Sci, Inst Math & Stat, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Stat, Inst Math & Stat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN GENETICS; v. 10, SEP 20 2019.
• Citações Web of Science: 0

Resumo

Faced with the lack of reliability and reproducibility in omics studies, more careful and robust methods are needed to overcome the existing challenges in the multi-omics analysis. In conventional omics data analysis, signal intensity values (denoted by M and values) are estimated neglecting pixel-level uncertainties, which may reflect noise and systematic artifacts. For example, intensity values from two-color microarray data are estimated by taking the mean or median of the pixel intensities within the spot and then subjected to a within-slide normalization by LOWESS. Thus, focusing on estimation and normalization of gene expression profiles, we propose a spot quantification method that takes into account pixel-level variability. Also, to preserve relevant variation that may be removed in LOWESS normalization with poorly chosen parameters, we propose a parameter selection method that is parsimonious and considers intrinsic characteristics of microarray data, such as heteroskedasticity. The usefulness of the proposed methods is illustrated by an application to real intestinal metaplasia data. Compared with the conventional approaches, the analysis is more robust and conservative, identifying fewer but more reliable differentially expressed genes. Also, the variability preservation allowed the identification of new differentially expressed genes. Using the proposed approach, we have identified differentially expressed genes involved in pathways in cancer and confirmed some molecular markers already reported in the literature. (AU)

• Processo FAPESP: 06/03227-2 - Expressão gênica em tumores do estômago e do esôfago: da biologia ao diagnóstico
• Beneficiário: Luiz Fernando Lima Reis
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/50761-2 - Modelos e métodos de e-Science para ciências da vida e agrárias
• Beneficiário: Roberto Marcondes Cesar Junior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/01587-0 - Armazenagem, modelagem e análise de sistemas dinâmicos para aplicações em e-Science
• Beneficiário: João Eduardo Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Programa eScience e Data Science - Temático