Publications by authors named "Alireza Karbalayghareh"

Identifying cell-type-specific 3D chromatin interactions between regulatory elements can help decipher gene regulation and interpret disease-associated non-coding variants. However, achieving this resolution with current 3D genomics technologies is often infeasible given limited input cell numbers. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps, including regulatory interactions, from single-cell ATAC sequencing (scATAC-seq) data alone.

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Article Synopsis
  • - This study identifies over 13 million interactions between transcriptional enhancers and their target genes across various cell types and tissues, which is crucial for understanding how gene regulation influences diseases.
  • - Utilizing a new predictive model called ENCODE-rE2G, the researchers achieved high accuracy in predicting enhancer-gene interactions, supported by a robust dataset from CRISPR experiments and genetic mapping.
  • - The findings highlight not only the role of enhancers and their contacts with promoters but also additional factors like promoter types and enhancer interactions that affect gene regulation, creating a detailed resource for future genetic research.
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The identification of cell-type-specific 3D chromatin interactions between regulatory elements can help to decipher gene regulation and to interpret the function of disease-associated non-coding variants. However, current chromosome conformation capture (3C) technologies are unable to resolve interactions at this resolution when only small numbers of cells are available as input. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps and regulatory interactions from single-cell ATAC sequencing (scATAC-seq) data alone.

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Recent deep learning models that predict the Hi-C contact map from DNA sequence achieve promising accuracy but cannot generalize to new cell types and or even capture differences among training cell types. We propose Epiphany, a neural network to predict cell-type-specific Hi-C contact maps from widely available epigenomic tracks. Epiphany uses bidirectional long short-term memory layers to capture long-range dependencies and optionally a generative adversarial network architecture to encourage contact map realism.

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Linking distal enhancers to genes and modeling their impact on target gene expression are longstanding unresolved problems in regulatory genomics and critical for interpreting noncoding genetic variation. Here, we present a new deep learning approach called GraphReg that exploits 3D interactions from chromosome conformation capture assays to predict gene expression from 1D epigenomic data or genomic DNA sequence. By using graph attention networks to exploit the connectivity of distal elements up to 2 Mb away in the genome, GraphReg more faithfully models gene regulation and more accurately predicts gene expression levels than the state-of-the-art deep learning methods for this task.

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There is often a limited amount of omics data to design predictive models in biomedicine. Knowing that these omics data come from underlying processes that may share common pathways and disease mechanisms, it may be beneficial for designing a more accurate and reliable predictor in a target domain of interest, where there is a lack of labeled data to leverage available data in relevant source domains. Here, we focus on developing Bayesian transfer learning methods for analyzing next-generation sequencing (NGS) data to help improve predictions in the target domain.

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Background: Expression-based phenotype classification using either microarray or RNA-Seq measurements suffers from a lack of specificity because pathway timing is not revealed and expressions are averaged across groups of cells. This paper studies expression-based classification under the assumption that single-cell measurements are sampled at a sufficient rate to detect regulatory timing. Thus, observations are expression trajectories.

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This paper studies classification of gene-expression trajectories coming from two classes, healthy and mutated (cancerous) using Boolean networks with perturbation (BNps) to model the dynamics of each class at the state level. Each class has its own BNp, which is partially known based on gene pathways. We employ a Gaussian model at the observation level to show the expression values of the genes given the hidden binary states at each time point.

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Gene-expression-based phenotype classification is used for disease diagnosis and prognosis relating to treatment strategies. The present paper considers classification based on sequential measurements of multiple genes using gene regulatory network (GRN) modeling. There are two networks, original and mutated, and observations consist of trajectories of network states.

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