In chronic diseases research, understanding and accounting for individual differences caused by genetic, environmental, and lifestyle factors have become increasingly important for successful disease management. Dynamic regression, as shown by recent work including ours, is a powerful technique to characterize and identify inhomogeneous associations that explain individual variability of disease progression. The overall ob- jective of this grant is to advance dynamic regression methodology to better meet the critical need of uncovering disease mechanism heterogeneity with improved capacity to handle longitudinal/survival outcomes and covariates in various complex forms (e.g. time-varying, high-dimensional, constrained). This application is motivated by our ongoing collaborations on Feeding Infants Right.. from the STart (FIRST) study. Under the overreaching goal to identify optimal care for infants with Cystic Fibrosis (CF), FIRST has systematically captured data on complete feeding history and longitudinally collected biomarkers (e.g. blood lipids and fecal microbiota) and accessed nutritional status and pulmonary disease throughout infancy. With the rich data collection, FIRST provides an unprecedented opportunity to exploit new sensible quanti?cations of early CF phenotype (e.g. pulmonary, growth) and their dynamic associations with observed factors (e.g. genotype, environmental factors); to assess breast/formula feeding schemes for CF infants; to ?ll in the information gap on the in?uence of biomarkers on growth and their relationships to feeding. The speci?c aims of this grant are to develop innovative and effective dynamic regression tools that can help achieve these impactful scienti?c goals: (1) We will investigate a sensible modeling perspective that focuses on subject-level latent characteristics (called latent individual risk feature (LIRF) hereafter) as a substantive re?ection of disease risk/status (e.g. length growth rate ). We will develop formal dynamic regression methods for delineating the heterogeneity in LIRF, which are not available in literature (Aim1). (2) We will develop an innovative survival dynamic regression strategy that enables a comprehensive assessment of the overall impact of time-dependent exposures (e.g. feeding history) on survival outcomes (e.g. time to pulmonary exacerbation). Current methods usually describe the effects of time-dependent covariates progressively over time and thus have limited utility for evaluating different feeding schemes (Aim2). (3) We will develop new dynamic regression approaches that give an integrative account of important data challenges/features (e.g. high-dimensionality, constraints, longitudinal outcomes, time-dependent covariates) for properly assessing the mechanisms/roles of biomarkers during CF infancy (Aim3). (4) The proposed statistical methods will be applied to FIRST and user-friendly software will be developed (Aims 4-5). Although speci?cally motivated by CF studies, the proposed methodologies are generally applicable to many other chronic diseases.

Public Health Relevance

We propose to develop ?exible and robust statistical methods to help decode the heterogeneity presented in chronic diseases, such as Cystic Fibrosis. The applications of the proposed methods will generate new knowledge to further the understanding of the mechanism and progression of chronic diseases that will lead to improved disease management strategies.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Sheridan, John T
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Emory University
Biostatistics & Other Math Sci
Schools of Public Health
United States
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Ma, Huijuan; Peng, Limin; Zhang, Zhumin et al. (2018) Generalized accelerated recurrence time model for multivariate recurrent event data with missing event type. Biometrics 74:954-965
Yang, Jing; Peng, Limin (2018) Estimating cross quantile residual ratio with left-truncated semi-competing risks data. Lifetime Data Anal 24:652-674
Zheng, Qi; Peng, Limin; He, Xuming (2018) HIGH DIMENSIONAL CENSORED QUANTILE REGRESSION. Ann Stat 46:308-343
Liu, Shuling; Manatunga, Amita K; Peng, Limin et al. (2017) A joint modeling approach for multivariate survival data with random length. Biometrics 73:666-677
Ong, Thida; Schechter, Michael; Yang, Jing et al. (2017) Socioeconomic Status, Smoke Exposure, and Health Outcomes in Young Children With Cystic Fibrosis. Pediatrics 139:
Zheng, Qi; Peng, Limin (2017) Consistent model identification of varying coefficient quantile regression with BIC tuning parameter selection. Commun Stat Theory Methods 46:1031-1049
Rahman, Akm Fazlur; Peng, Limin; Manatunga, Amita et al. (2017) Nonparametric Regression Method for Broad Sense Agreement. J Nonparametr Stat 29:280-300
Li, Ruosha; Peng, Limin (2017) Assessing quantile prediction with censored quantile regression models. Biometrics 73:517-528
Limoli, D H; Yang, J; Khansaheb, M K et al. (2016) Staphylococcus aureus and Pseudomonas aeruginosa co-infection is associated with cystic fibrosis-related diabetes and poor clinical outcomes. Eur J Clin Microbiol Infect Dis 35:947-53
Sun, Xiaoyan; Peng, Limin; Manatunga, Amita et al. (2016) Quantile regression analysis of censored longitudinal data with irregular outcome-dependent follow-up. Biometrics 72:64-73

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