My Nguyen

Brydon P. G. Wall, My Nguyen, J. Chuck Harrell et al.

Three-Dimensional (3D) chromatin interactions, such as enhancer-promoter interactions (EPIs), loops, Topologically Associating Domains (TADs), and A/B compartments play critical roles in a wide range of cellular processes by regulating gene expression. Recent development of chromatin conformation capture technologies has enabled genome-wide profiling of various 3D structures, even with single cells. However, current catalogs of 3D structures remain incomplete and unreliable due to differences in technology, tools, and low data resolution. Machine learning methods have emerged as an alternative to obtain missing 3D interactions and/or improve resolution. Such methods frequently use genome annotation data (ChIP-seq, DNAse-seq, etc.), DNA sequencing information (k-mers, Transcription Factor Binding Site (TFBS) motifs), and other genomic properties to learn the associations between genomic features and chromatin interactions. In this review, we discuss computational tools for predicting three types of 3D interactions (EPIs, chromatin interactions, TAD boundaries) and analyze their pros and cons. We also point out obstacles of computational prediction of 3D interactions and suggest future research directions.

Amy Armento Lee, Narayan Hegde, Nina Deliu et al.

Consistent physical inactivity poses a major global health challenge. Mobile health (mHealth) interventions, particularly Just-in-Time Adaptive Interventions (JITAIs), offer a promising avenue for scalable, personalized physical activity (PA) promotion. However, developing and evaluating such interventions at scale, while integrating robust behavioral science, presents methodological hurdles. The PEARL study was the first large-scale, four-arm randomized controlled trial to assess a reinforcement learning (RL) algorithm, informed by health behavior change theory, to personalize the content and timing of PA nudges via a Fitbit app. We enrolled and randomized 13,463 Fitbit users into four study arms: control, random, fixed, and RL. The control arm received no nudges. The other three arms received nudges from a bank of 155 nudges based on behavioral science principles. The random arm received nudges selected at random. The fixed arm received nudges based on a pre-set logic from survey responses about PA barriers. The RL group received nudges selected by an adaptive RL algorithm. We included 7,711 participants in primary analyses (mean age 42.1, 86.3% female, baseline steps 5,618.2). We observed an increase in PA for the RL group compared to all other groups from baseline to 1 and 2 months. The RL group had significantly increased average daily step count at 1 month compared to all other groups: control (+296 steps, p=0.0002), random (+218 steps, p=0.005), and fixed (+238 steps, p=0.002). At 2 months, the RL group sustained a significant increase compared to the control group (+210 steps, p=0.0122). Generalized estimating equation models also revealed a sustained increase in daily steps in the RL group vs. control (+208 steps, p=0.002). These findings demonstrate the potential of a scalable, behaviorally-informed RL approach to personalize digital health interventions for PA.