# CORE B: Computational Biology and Statistical Modeling

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2022 · $157,640

## Abstract

Computational Biology and Statistical Modeling Core (CORE B)
(University of California, Berkeley)
SUMMARY
The Computational Biology and Statistical Modeling Core (Core B) will provide essential services to
individual Projects and the Program Project (P01) as a whole by providing statistical support at each stage of
research. Critically, Core B will enable the Projects to address key themes of the P01 by applying unifying
computational biology, statistical, and machine learning approaches to study natural and vaccine-induced
dengue humoral and cellular immunity. In Aim 1, Core B will conduct epidemiological analyses of the natural
dengue virus (DENV) infection and dengue vaccine cohorts to inform the immunological studies proposed by
Projects 1, 2, and 3. For the Nicaragua Pediatric Dengue Cohort Study, we will work closely with Core C to
investigate dengue incidence before and after the introduction of Zika as well as how changing DENV
transmission intensity affects dengue disease severity. For the Cebu Dengvaxia® cohort, we will estimate DENV
infection and dengue disease incidence stratified by baseline DENV serostatus and vaccination history to support
the immune correlates studies proposed by Project 2. We will also compare these two pediatric cohorts to
understand how geography, DENV transmission intensity, ZIKV infection history, and serotype prevalence affect
dengue disease. Phylogenetic and phylodynamic analyses will be conducted for all DENV isolates from both
cohorts. In Aim 2, we will support each Project individually and conduct cross-Project analyses to identify
immune markers that correlate with protection against symptomatic dengue and pathogenesis of severe dengue
disease. This aim encompasses immune correlates of natural and vaccine-induced DENV immunity. We will
work with each Project to design case-control studies to test how DENV-specific serum antibody, B cell, and T
cell characteristics predict distinct clinical outcomes. Core B will analyze the multi-dimensional datasets
produced by the Projects to classify clinical outcomes using straightforward machine learning methods such as
generalized linear models, flexible approaches such as random forests, and methods that are robust to outliers
such as support vector machines, all with regularization to reduce model complexity. In Aim 3, we will support
the Projects in studying children who have experienced natural primary and secondary DENV infections to
identify immune markers that predict maintenance anti-DENV immunity. We will use regression models to
determine how antibody and helper T cell characteristics measured soon after infection predict both the
magnitude and the durability of cross-reactive and type-specific antibody responses. We will then incorporate
the predictive immune markers into linear and more flexible mixed-effects regression models to fit antibody
dynamics following primary and secondary DENV infection. Parallel analyses will be conducted for baseline
serone...

## Key facts

- **NIH application ID:** 10458126
- **Project number:** 5P01AI106695-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Leah Katzelnick
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $157,640
- **Award type:** 5
- **Project period:** 2015-07-29 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458126

## Citation

> US National Institutes of Health, RePORTER application 10458126, CORE B: Computational Biology and Statistical Modeling (5P01AI106695-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10458126. Licensed CC0.

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