Over the past decade, methods for predicting three-dimensional (3-D) chromosome and genome structures have proliferated. This has been primarily due to the development of high-throughput, next-generation chromosome conformation capture (3C) technologies, which have provided next-generation sequencing data about chromosome conformations in order to map the 3-D genome structure. The introduction of the Hi-C technique—a variant of the 3C method—has allowed researchers to extract the interaction frequency (IF) for all loci of a genome at high-throughput and at a genome-wide scale. In this review we describe, categorize, and compare the various methods developed to map chromosome and genome structures from 3C data—particularly Hi-C data. We summarize the improvements introduced by these methods, describe the approach used for method evaluation, and discuss how these advancements shape the future of genome structure construction.
Chromatin conformation plays an important role in a variety of genomic processes. Hi-C is one of the most popular assays for inspecting chromatin conformation. However, the utility of Hi-C contact maps is bottlenecked by resolution. Here we present VEHiCLE, a deep learning algorithm for resolution enhancement of Hi-C contact data. VEHiCLE utilises a variational autoencoder and adversarial training strategy equipped with four loss functions (adversarial loss, variational loss, chromosome topology-inspired insulation loss, and mean square error loss) to enhance contact maps, making them more viable for downstream analysis. VEHiCLE expands previous efforts at Hi-C super resolution by providing novel insight into the biologically meaningful and human interpretable feature extraction. Using a deep variational autoencoder, VEHiCLE provides a user tunable, full generative model for generating synthetic Hi-C data while also providing state-of-the-art results in enhancement of Hi-C data across multiple metrics.
Cryo-electron microscopy (Cryo-EM) is widely used in the determination of the three-dimensional (3D) structures of macromolecules. Particle picking from 2D micrographs remains a challenging early step in the Cryo-EM pipeline due to the diversity of particle shapes and the extremely low signal-to-noise ratio (SNR) of micrographs. Because of these issues,
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