Tanmayee Narendra

Epigenetic modifications are dynamic mechanisms involved in the regulation of gene expression. Unlike the DNA sequence, epigenetic patterns vary not only between individuals, but also between different cell types within an individual. Environmental factors, somatic mutations and ageing contribute to epigenetic changes that may constitute early hallmarks or causal factors of disease. Epigenetic modifications are reversible and thus promising therapeutic targets for precision medicine. However, mapping efforts to determine an individual’s cell-type-specific epigenome are constrained by experimental costs and tissue accessibility. To address these challenges, we developed eDICE, an attention-based deep learning model that is trained to impute missing epigenomic tracks by conditioning on observed tracks. Using a recently published set of epigenomes from four individual donors, we show that transfer learning across individuals allows eDICE to successfully predict individual-specific epigenetic variation even in tissues that are unmapped in a given donor. These results highlight the potential of machine learning-based imputation methods to advance personalized epigenomics.

Causal discovery, i.e., inferring underlying causal relationships from observational data, is highly challenging for AI systems. In a time series modeling context, traditional causal discovery methods mainly consider constrained scenarios with fully observed variables and/or data from stationary time-series. We develop a causal discovery approach to handle a wide class of nonstationary time series that are conditionally stationary, where the nonstationary behaviour is modeled as stationarity conditioned on a set of latent state variables. Named State-Dependent Causal Inference (SDCI), our approach is able to recover the underlying causal dependencies, with provable identifiablity for the state-dependent causal structures. Empirical experiments on nonlinear particle interaction data and gene regulatory networks demonstrate SDCI’s superior performance over baseline causal discovery methods. Improved results over non-causal RNNs on modeling NBA player movements demonstrate the potential of our method and motivate the use of causality-driven methods for forecasting.

Epigenetic mechanisms enable cellular differentiation and the maintenance of distinct cell types. They enable rapid responses to external signals through changes in gene regulation and their registration over longer time spans. Consequently, the chromatin landscape, which is the overall organization and biochemical state of chromatin, exhibits both cell-type and individual specificity and contributes to phenotypic diversity. Genomic distributions of chromatin features are typically measured using chromatin immunoprecipitation sequencing and related methods. However, these measurements are subject to substantial biases introduced by the chromatin landscape itself. Here, we introduce DecoDen, which uses measurements of several different histone modifications, to simultaneously learn shared chromatin landscapes while de-biasing individual measurement tracks. We demonstrate DecoDen’s effectiveness on an integrative analysis of histone modification patterns across multiple tissues in personal epigenomes. DecoDen is available at https://github.com/ntanmayee/decoden.

Motivation Time-series single-cell transcriptomics enables the study of dynamic gene regulation. However, standard computational tools frequently aggregate temporal data into static, dense topologies, obscuring the precise regulatory rewiring that drives developmental transitions. Further, navigating the inherent noise of statistical inference without losing biological interpretability remains an important bottleneck. Results We present Tangerine, a Python framework for the dynamic reconstruction and interactive exploration of time-varying gene regulatory networks. Tangerine integrates time-constrained metacell aggregation with regularized linear modelling and non-parametric correlation to infer dynamic topologies. To solve the interpretability gap, it features a browser-based visual analytics engine. Tangerine empowers researchers to track macroscopic gene module evolution, interactively filter effect sizes, and link topological rewiring directly to raw transcriptomic evidence. Availability and implementation Tangerine is implemented in Python and Plotly Dash. The code is available on Github at https://github.com/ntanmayee/tangerine.