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
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.
基金:
This work was supported in part by research grants from USA
National Institutes of Health (R03-DE025646), National Natural
Science Foundation of China (81673448, 81670191), Natural
Science Foundation of Jiangsu Province China (BK20161218,
BK20161223) and The Applied Basic Research Programs of Suzhou
City (SYS201546).
语种:
外文
被引次数:
WOS:
PubmedID:
中科院(CAS)分区:
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
JCR分区:
出版当年[2016]版:
Q1BIOCHEMICAL RESEARCH METHODSQ1MATHEMATICAL & COMPUTATIONAL BIOLOGYQ1BIOTECHNOLOGY & APPLIED MICROBIOLOGY
最新[2024]版:
Q1BIOCHEMICAL RESEARCH METHODSQ1BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ1MATHEMATICAL & COMPUTATIONAL BIOLOGY
第一作者机构:[1]Department of Biostatistics, Jiann-Ping Hsu College of Public Health, Georgia Southern University, Statesboro, GA, USA,
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Xinyan Zhang,Bingzong Li,Huiying Han,et al.Pathway-structured predictive modeling for multi-level drug response in multiple myeloma[J].BIOINFORMATICS.2018,34(21):3609-3615.doi:10.1093/bioinformatics/bty436.
APA:
Xinyan Zhang,Bingzong Li,Huiying Han,Sha Song,Hongxia Xu...&Nengjun Yi.(2018).Pathway-structured predictive modeling for multi-level drug response in multiple myeloma.BIOINFORMATICS,34,(21)
MLA:
Xinyan Zhang,et al."Pathway-structured predictive modeling for multi-level drug response in multiple myeloma".BIOINFORMATICS 34..21(2018):3609-3615