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      IChrom-Deep: An Attention-Based Deep Learning Model for Identifying Chromatin Interactions.

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          Abstract

          Identification of chromatin interactions is crucial for advancing our knowledge of gene regulation. However, due to the limitations of high-throughput experimental techniques, there is an urgent need to develop computational methods for predicting chromatin interactions. In this study, we propose a novel attention-based deep learning model, termed IChrom-Deep, to identify chromatin interactions using sequence features and genomic features. The experimental results based on the datasets of three cell lines demonstrate that the IChrom-Deep achieves satisfactory performance and is superior to the previous methods. We also investigate the effect of DNA sequence and associated features and genomic features on chromatin interactions, and highlight the applicable scenarios of some features, such as sequence conservation and distance. Moreover, we identify a few genomic features that are extremely important across different cell lines, and IChrom-Deep achieves comparable performance with only these significant genomic features versus using all genomic features. It is believed that IChrom-Deep can serve as a useful tool for future studies that seek to identify chromatin interactions.

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          Most cited references57

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          Is Open Access

          BEDTools: a flexible suite of utilities for comparing genomic features

          Motivation: Testing for correlations between different sets of genomic features is a fundamental task in genomics research. However, searching for overlaps between features with existing web-based methods is complicated by the massive datasets that are routinely produced with current sequencing technologies. Fast and flexible tools are therefore required to ask complex questions of these data in an efficient manner. Results: This article introduces a new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format. BEDTools also supports the comparison of sequence alignments in BAM format to both BED and GFF features. The tools are extremely efficient and allow the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks. BEDTools can be combined with one another as well as with standard UNIX commands, thus facilitating routine genomics tasks as well as pipelines that can quickly answer intricate questions of large genomic datasets. Availability and implementation: BEDTools was written in C++. Source code and a comprehensive user manual are freely available at http://code.google.com/p/bedtools Contact: aaronquinlan@gmail.com; imh4y@virginia.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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            Comprehensive mapping of long-range interactions reveals folding principles of the human genome.

            We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.
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              Focal loss for dense object detection

              The highest accuracy object detectors to date are based on a two-stage approach popularized by R-CNN, where a classifier is applied to a sparse set of candidate object locations. In contrast, one-stage detectors that are applied over a regular, dense sampling of possible object locations have the potential to be faster and simpler, but have trailed the accuracy of two-stage detectors thus far. In this paper, we investigate why this is the case. We discover that the extreme foreground-background class imbalance encountered during training of dense detectors is the central cause. We propose to address this class imbalance by reshaping the standard cross entropy loss such that it down-weights the loss assigned to well-classified examples. Our novel Focal Loss focuses training on a sparse set of hard examples and prevents the vast number of easy negatives from overwhelming the detector during training. To evaluate the effectiveness of our loss, we design and train a simple dense detector we call RetinaNet. Our results show that when trained with the focal loss, RetinaNet is able to match the speed of previous one-stage detectors while surpassing the accuracy of all existing state-of-the-art two-stage detectors. Code is at: https://github.com/facebookresearch/Detectron.
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                Author and article information

                Journal
                IEEE J Biomed Health Inform
                IEEE journal of biomedical and health informatics
                Institute of Electrical and Electronics Engineers (IEEE)
                2168-2208
                2168-2194
                Sep 2023
                : 27
                : 9
                Article
                10.1109/JBHI.2023.3292299
                37402191
                91a10d94-76e3-46a9-b8b4-4fe3e057f447
                History

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