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Pathway-structured predictive modeling for multi-level drug response in multiple myeloma

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机构: [1]Department of Biostatistics, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA, [2]Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, China, [3]Department of Cell Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China, [4]School of Medicine, Eastern Virginia Medical School, Norfork, VA 23507, USA [5]Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Motivation: Molecular analyses suggest that myeloma is composed of distinct sub-types that have different molecular pathologies and various response rates to certain treatments. Drug responses in multiple myeloma (MM) are usually recorded as a multi-level ordinal outcome. One of the goals of drug response studies is to predict which response category any patients belong to with high probability based on their clinical and molecular features. However, as most of genes have small effects, gene-based models may provide limited predictive accuracy. In that case, methods for predicting multi-level ordinal drug responses by incorporating biological pathways are desired but have not been developed yet. Results: We propose a pathway-structured method for predicting multi-level ordinal responses using a two-stage approach. We first develop hierarchical ordinal logistic models and an efficient quasi-Newton algorithm for jointly analyzing numerous correlated variables. Our two-stage approach first obtains the linear predictor (called the pathway score) for each pathway by fitting all predictors within each pathway using the hierarchical ordinal logistic approach, and then combines the pathway scores as new predictors to build a predictive model. We applied the proposed method to two publicly available datasets for predicting multi-level ordinal drug responses in MM using large-scale gene expression data and pathway information. Our results show that our approach not only significantly improved the predictive performance compared with the corresponding gene-based model but also allowed us to identify biologically relevant pathways.

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出版当年[2017]版:
大类 | 2 区 生物
小类 | 1 区 数学与计算生物学 2 区 生化研究方法 2 区 生物工程与应用微生物
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 生化研究方法 3 区 生物工程与应用微生物 3 区 数学与计算生物学
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出版当年[2016]版:
Q1 BIOCHEMICAL RESEARCH METHODS Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
最新[2024]版:
Q1 BIOCHEMICAL RESEARCH METHODS Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 MATHEMATICAL & COMPUTATIONAL BIOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2016版] 出版当年五年平均 出版前一年[2015版] 出版后一年[2017版]

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第一作者机构: [1]Department of Biostatistics, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA,
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通讯机构: [3]Department of Cell Biology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China, [5]Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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