Carolyn Huang | Searcharxiv

arXiv2026

A Modular Mechanistic In Silico Model for In Vitro Transcription Process Yield and Product Quality Prediction

In vitro transcription (IVT) plays a critical role in the manufacture of mRNA vaccines and therapeutics. Optimizing mRNA yield and ensuring product quality, such as capping efficiency and integrity, are essential but mechanistically complex. This study presents a modular mechanistic model of the IVT process to advance scientific understanding and improve predictive capability. The IVT reaction network is decomposed into interconnected modules describing (1) initiation and capping, (2) elongation and truncation, (3) termination and read-through, (4) mRNA degradation, (5) magnesium pyrophosphate precipitation, and (6) enzymatic degradation of pyrophosphate. Guided by biochemical principles and experimental data, kinetic models were developed for each module, accounting for mass balances, molecular complexation, and enzyme activity, and were subsequently assembled to capture coupled IVT dynamics. Multivariate residual analysis and Shapley value-based sensitivity analysis, guided by domain knowledge, were applied to iteratively improve model fidelity. These machine learning-driven analytics enabled identification of key mechanisms, supported in silico experimentation, and facilitated root-cause analysis. Combined with Gaussian-process-based batch Bayesian optimization for efficient parameter estimation, this framework establishes a scalable hybrid (mechanistic + machine learning) modeling platform that integrates heterogeneous data, accelerates model calibration, and supports rational design and optimization of mRNA manufacturing processes.

q-bio.MN↗

arXiv2023

ADVISE: AI-accelerated Design of Evidence Synthesis for Global Development

When designing evidence-based policies and programs, decision-makers must distill key information from a vast and rapidly growing literature base. Identifying relevant literature from raw search results is time and resource intensive, and is often done by manual screening. In this study, we develop an AI agent based on a bidirectional encoder representations from transformers (BERT) model and incorporate it into a human team designing an evidence synthesis product for global development. We explore the effectiveness of the human-AI hybrid team in accelerating the evidence synthesis process. To further improve team efficiency, we enhance the human-AI hybrid team through active learning (AL). Specifically, we explore different sampling strategies, including random sampling, least confidence (LC) sampling, and highest priority (HP) sampling, to study their influence on the collaborative screening process. Results show that incorporating the BERT-based AI agent into the human team can reduce the human screening effort by 68.5% compared to the case of no AI assistance and by 16.8% compared to the case of using a support vector machine (SVM)-based AI agent for identifying 80% of all relevant documents. When we apply the HP sampling strategy for AL, the human screening effort can be reduced even more: by 78.3% for identifying 80% of all relevant documents compared to no AI assistance. We apply the AL-enhanced human-AI hybrid teaming workflow in the design process of three evidence gap maps (EGMs) for USAID and find it to be highly effective. These findings demonstrate how AI can accelerate the development of evidence synthesis products and promote timely evidence-based decision making in global development in a human-AI hybrid teaming context.

cs.CL↗