The human genome runs to 3bn pairs of letters - the Gs, Ts, Cs and As that comprise the DNA code. The human genome runs to 3bn pairs of letters - the Gs, Ts, Cs and As that comprise the DNA code. Researchers at Google DeepMind have unveiled their latest artificial intelligence tool and claimed it will help scientists identify the genetic drivers of disease and ultimately pave the way for new treatments. AlphaGenome predicts how mutations interfere with the way genes are controlled, changing when they are switched on, in which cells of the body, and whether their biological volume controls are set to high or low. Most common diseases that run in families, including heart disease and autoimmune disorders, as well as mental health problems, have been linked to mutations that affect gene regulation, as have many cancers, but identifying which genetic glitches are to blame is far from straightforward.

The past decade has seen a revolution in genomic technologies that enabled a flood of genome-wide profiling of chromatin marks. Recent literature tried to understand gene regulation by predicting gene expression from large-scale chromatin measurements. Two fundamental challenges exist for such learning tasks: (1) genome-wide chromatin signals are spatially structured, high-dimensional and highly modular; and (2) the core aim is to understand what are the relevant factors and how they work together. Previous studies either failed to model complex dependencies among input signals or relied on separate feature analysis to explain the decisions. This paper presents an attention-based deep learning approach; AttentiveChrome, that uses a unified architecture to model and to interpret dependencies among chromatin factors for controlling gene regulation. AttentiveChrome uses a hierarchy of multiple Long Short-Term Memory (LSTM) modules to encode the input signals and to model how various chromatin marks cooperate automatically. AttentiveChrome trains two levels of attention jointly with the target prediction, enabling it to attend differentially to relevant marks and to locate important positions per mark. We evaluate the model across 56 different cell types (tasks) in human. Not only is the proposed architecture more accurate, but its attention scores also provide a better interpretation than state-of-the-art feature visualization methods such as saliency map.

The past decade has seen a revolution in genomic technologies that enabled a flood of genome-wide profiling of chromatin marks. Recent literature tried to understand gene regulation by predicting gene expression from large-scale chromatin measurements.

Modern high-throughput biological datasets with thousands of perturbations provide the opportunity for large-scale discovery of causal graphs that represent the regulatory interactions between genes. Numerous methods have been proposed to infer a directed acyclic graph (DAG) corresponding to the underlying gene regulatory network (GRN) that captures causal gene relationships. However, existing models have restrictive assumptions (e.g. linearity, acyclicity), limited scalability, and/or fail to address the dynamic nature of biological processes such as cellular differentiation. We propose PerturbODE, a novel framework that incorporates biologically informative neural ordinary differential equations (neural ODEs) to model cell state trajectories under perturbations and derive the causal GRN from the neural ODE's parameters. We demonstrate PerturbODE's efficacy in trajectory prediction and GRN inference across simulated and real over-expression datasets.

The paper presents a novel method for predicting gene regulation by LSTM with an attention mechanism. The model consists of two levels, where the first level is applied on bins for each histone modifications (HM) and the second level is applied to multiple HMs. Attention mechanism is used in each level to focus on the important parts of the bins and HMs. In the experiments, the proposed method improves AUC scores over baseline models including CNN, LSTM, and CNN with an attention mechanism. This is an interesting paper which shows that LSTM with an attention mechanism can predict gene regulation.

Neural Information Processing Systems http://nips.cc/

Unraveling the complexities of Gene Regulatory Networks (GRNs) is crucial for understanding cellular processes and disease mechanisms. Traditional computational methods often struggle with the dynamic nature of these networks. This study explores the use of Graph Neural Networks (GNNs), a powerful approach for modeling graph-structured data like GRNs. Utilizing a Graph Attention Network v2 (GATv2), our study presents a novel approach to the construction and interrogation of GRNs, informed by gene expression data and Boolean models derived from literature. The model's adeptness in accurately predicting regulatory interactions and pinpointing key regulators is attributed to advanced attention mechanisms, a hallmark of the GNN framework. These insights suggest that GNNs are primed to revolutionize GRN analysis, addressing traditional limitations and offering richer biological insights. The success of GNNs, as highlighted by our model's reliance on high-quality data, calls for enhanced data collection methods to sustain progress. The integration of GNNs in GRN research is set to pioneer developments in personalized medicine, drug discovery, and our grasp of biological systems, bolstered by the structural analysis of networks for improved node and edge prediction.

Artificial intelligence (AI) models based on deep learning now represent the state of the art for making functional predictions in genomics research. However, the underlying basis on which predictive models make such predictions is often unknown. For genomics researchers, this missing explanatory information would frequently be of greater value than the predictions themselves, as it can enable new insights into genetic processes. We review progress in the emerging area of explainable AI (xAI), a field with the potential to empower life science researchers to gain mechanistic insights into complex deep learning models. We discuss and categorize approaches for model interpretation, including an intuitive understanding of how each approach works and their underlying assumptions and limitations in the context of typical high-throughput biological datasets. In this Review, the authors describe advances in deep learning approaches in genomics, whereby researchers are moving beyond the typical ‘black box’ nature of models to obtain biological insights through explainable artificial intelligence (xAI).

Histone modifications play a critical role in gene regulation. Consequently, predicting gene expression from histone modification signals is a highly motivated problem in epigenetics. We build upon the work of DeepChrome by Singh et al. (2016), who trained classifiers that map histone modification signals to gene expression. We present a novel visualization technique for providing insight into combinatorial relationships among histone modifications for gene regulation that uses a generative adversarial network to generate histone modification signals. We also explore and compare various architectural changes, with results suggesting that the 645k-parameter convolutional neural network from DeepChrome has the same predictive power as a 12-parameter linear network. Results from cross-cell prediction experiments, where the model is trained and tested on datasets of varying sizes, cell-types, and correlations, suggest the relationship between histone modification signals and gene expression is independent of cell type. We release our PyTorch re-implementation of DeepChrome on GitHub \footnote{\url{github.com/ssss1029/gene_expression_294}}.\parfillskip=0pt

Scientists have developed an artificial intelligence (AI)-based neural network model that accurately predicts gene expression in yeast. The team has validated the ability of its neural network in high-throughput experiments and the work opens doors for a broad spectrum of scientific questions. The model can help design genes with customized levels of expression for the development of gene therapies or industrial applications and clarify evolutionary mechanisms that regulate gene expression. The findings were published in the journal Nature, in an article titled, "The evolution, evolvability, and engineering of gene regulatory DNA." "This work highlights what possibilities open up when we design new kinds of experiments to generate the right data to train models," said Aviv Regev, PhD, a professor of biology at MIT, core member of the Broad Institute of Harvard and MIT, head of Genentech Research and Early Development, and the senior author of the study. The researchers employed two key technologies to predict gene expression in the yeast Saccharomyces cerevisiae.