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Motivation Hi-C is a genome-wide technology for investigating 3D chromatin conformation by measuring physical contacts between pairs of genomic regions. The resolution of Hi-C data directly impacts the effectiveness and accuracy of downstream analysis such as identifying topologically associating domains (TADs) and meaningful chromatin loops. High resolution Hi-C data are valuable resources which implicate the relationship between 3D genome conformation and function, especially linking distal regulatory elements to their target genes. However, high resolution Hi-C data across various tissues and cell types are not always available due to the high sequencing cost. It is therefore indispensable to develop computational approaches for enhancing the resolution of Hi-C data. Results We proposed hicGAN, an open-sourced framework, for inferring high resolution Hi-C data from low resolution Hi-C data with generative adversarial networks (GANs). To the best of our knowledge, this is the first study to apply GANs to 3D genome analysis. We demonstrate that hicGAN effectively enhances the resolution of low resolution Hi-C data by generating matrices that are highly consistent with the original high resolution Hi-C matrices. A typical scenario of usage for our approach is to enhance low resolution Hi-C data in new cell types, especially where the high resolution Hi-C data are not available. Our study not only presents a novel approach for enhancing Hi-C data resolution, but also provides fascinating insights into disclosing complex mechanism underlying the formation of chromatin contacts. Availability and implementation We release hicGAN as an open-sourced software at https://github.com/kimmo1019/hicGAN. Supplementary information Supplementary data are available at Bioinformatics online.

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We propose a joint segmentation and classification deep model for early glaucoma diagnosis using retina imaging with optical coherence tomography (OCT). Our motivation roots in the observation that ophthalmologists make the clinical decision by analyzing the retinal nerve fiber layer (RNFL) from OCT images. To simulate this process, we propose a novel deep model that joins the retinal layer segmentation and glaucoma classification. Our model consists of three parts. First, the segmentation network simultaneously predicts both six retinal layers and five boundaries between them. Then, we introduce a post processing algorithm to fuse the two results while enforcing the topology correctness. Finally, the classification network takes the RNFL thickness vector as input and outputs the probability of being glaucoma. In the classification network, we propose a carefully designed module to implement the clinical strategy to diagnose glaucoma. We validate our method both in a collected dataset of 1004 circular OCT B-Scans from 234 subjects and in a public dataset of 110 B-Scans from 10 patients with diabetic macular edema. Experimental results demonstrate that our method achieves superior segmentation performance than other state-of-the-art methods both in our collected dataset and in public dataset with severe retina pathology. For glaucoma classification, our model achieves diagnostic accuracy of 81.4% with AUC of 0.864, which clearly outperforms baseline methods.

Motivation: Quantitative detection of histone modifications has emerged in the recent years in a major means for understanding such biological processes as chromosome packaging, transcriptional activation, and DNA damage. However, high-throughput experimental techniques such as ChIP-seq are usually expensive and time-consuming, prohibiting the establishment of a histone modification landscape for hundreds of cell types across dozens of histone markers. These disadvantages have been appealing for computational methods to complement experimental approaches towards large-scale analysis of histone modifications. Results: We proposed a deep learning framework to integrate sequence information and chromatin accessibility data for the accurate prediction of modification sites specific to different histone markers. Our method, named DeepHistone, outperformed several baseline methods in a series of comprehensive validation experiments, not only within an epigenome but also across epigenomes. Besides, sequence signatures automatically extracted by our method was consistent with known transcription factor binding sites, thereby giving insights into regulatory signatures of histone modifications. As an application, our method was shown to be able to distinguish functional single nucleotide polymorphisms from their nearby genetic variants, thereby having the potential to be used for exploring functional implications of putative disease-associated genetic variants. Conclusions: DeepHistone demonstrated the possibility of using a deep learning framework to integrate DNA sequence and experimental data for predicting epigenomic signals. With the state-of-the-art performance, DeepHistone was expected to shed light on a variety of epigenomic studies.

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Motivation Quantitative detection of histone modifications has emerged in the recent years as a major means for understanding such biological processes as chromosome packaging, transcriptional activation, and DNA damage. However, high-throughput experimental techniques such as ChIP-seq are usually expensive and time-consuming, prohibiting the establishment of a histone modification landscape for hundreds of cell types across dozens of histone markers. These disadvantages have been appealing for computational methods to complement experimental approaches towards large-scale analysis of histone modifications. Results We proposed a deep learning framework to integrate sequence information and chromatin accessibility data for the accurate prediction of modification sites specific to different histone markers. Our method, named DeepHistone, outperformed several baseline methods in a series of comprehensive validation experiments, not only within an epigenome but also across epigenomes. Besides, sequence signatures automatically extracted by our method was consistent with known transcription factor binding sites, thereby giving insights into regulatory signatures of histone modifications. As an application, our method was shown to be able to distinguish functional single nucleotide polymorphisms from their nearby genetic variants, thereby having the potential to be used for exploring functional implications of putative disease-associated genetic variants. Conclusions DeepHistone demonstrated the possibility of using a deep learning framework to integrate DNA sequence and experimental data for predicting epigenomic signals. With the state-of-the-art performance, DeepHistone was expected to shed light on a variety of epigenomic studies. DeepHistone is freely available in https://github.com/QijinYin/DeepHistone .