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Biology subjects

Highsmith, M. R.

Publications and source records attributed to Highsmith, M. R..

6 recordsLinked to original sources

TAPIOCA: Topological Attention and Predictive Inference of Chromatin Arrangement Using Epigenetic Features

Chromatin conformation is an important characteristic of the genome which has been repeatedly demonstrated to play vital roles in many biological processes. Chromatin can be characterized by the presence or absence of structural motifs called topologically associated domains. The de facto strategy for determination of topologically associated domains within a cell line is the use of Hi-C sequencing data. However Hi-C sequencing data can be expensive or otherwise unavailable. Various epigenetic features have been hypothesized to contribute to the determination of chromatin conformation. Here we present TAPIOCA, a self-attention based deep learning transformer algorithm for the prediction of chromatin topology which circumvents the need for labeled Hi-C data and makes effective predictions of chromatin conformation organization using only epigenetic features. TAPIOCA outperforms prior art in established metrics of TAD prediction, while generalizing across cell lines beyond those used in training. Availabilitythe source code of TAPIOCA and training and test datasets are available at https://github.com/Max-Highsmith/TAPIOCA Author SummaryIn this paper we outline a machine learning approach for predicting the topological organization of chromosomes using epigenetic track data as features. By utilizing an architecture inspired by the sequence transduction transformer network we are able to effectively predict multiple metrics used to characterize topologically associated domains. Our experimental results demonstrate that once trained our algorithm can effectively predict topological organization on novel cell lines all without any exposure to original Hi-C data in test datasets.

genomics↗

VEHiCLE: a Variationally Encoded Hi-C Loss Enhancement algorithm

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 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 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.

genomics↗

Prediction of the 4D Chromosome Structure From Time-Series Hi-C Data

Chromatin conformation plays an important role in a variety of genomic processes. Hi-C Data is frequently used to analyse structural features of chromatin such as AB compartments, topologically associated domains, and 3D structural models. Recently the genomics community has displayed growing interest in chromatin dynamics over time. Here we present 4DMax, a novel method which uses time-series Hi-C data to predict dynamic chromosome conformation. Using both synthetic data and real time-series Hi-C data from processes such as induced pluripotent stem cell reprogramming and cardiomyocyte differentiation, we construct fluid four dimensional models of individual chromosomes. These predicted 4D models effectively interpolate chromatin position across time, permitting prediction of unknown Hi-C contact maps at intermittent time points. Our results demonstrate that 4DMax correctly recovers higher order features of chromatin such as AB compartments and topologically associated domains, even at time points where Hi-C data is not made available to the algorithm. Use of 4DMax may alleviate the cost of expensive Hi-C experiments by interpolating intermediary timepoints while also providing valuable visualization of dynamic chromatin changes.

genomics↗

DeepCryoPicker: Fully Automated Deep Neural Network for Single Protein Particle Picking in cryo-EM

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, significant human intervention is often required to generate a high-quality set of particles for input to the downstream structure determination steps. Here we propose a fully automated approach (DeepCryoPicker) for single particle picking based on deep learning. It first uses automated unsupervised learning to generate particle training datasets. Then it trains a deep neural network to classify particles automatically. Results indicate that the DeepCryoPicker compares favorably with semi-automated methods such as DeepEM, DeepPicker and RELION, with the significant advantage of not requiring human intervention.

bioinformatics↗

Deep Learning For Denoising Hi-C Chromosomal Contact Data

MotivationThe three-dimensional (3D) organization of an organisms genome and chromosomes plays a significant role in many biological processes. Currently, methods exist for modeling chromosomal 3D structure using contact matrices generated via chromosome conformation capture (3C) techniques such as Hi-C. However, the effectiveness of these methods is inherently bottlenecked by the quality of the Hi-C data, which may be corrupted by experimental noise. Consequently, it is valuable to develop methods for eliminating the impact of noise on the quality of reconstructed structures.\n\nResultsWe develop unsupervised and semi-supervised deep learning algorithms (i.e. deep convolutional autoencoders) to denoise Hi-C contact matrix data and improve the quality of chromosome structure predictions. When applied to noisy synthetic contact matrices of the yeast genome, our network demonstrates consistent improvement across metrics for contact matrix similarity including: Pearson Correlation, Spearman Correlation and Signal-to-Noise Ratio. Positive improvement across these metrics is seen consistently across a wide space of parameters to both gaussian and poisson noise functions.\n\nContactmrh8x5@mail.missouri.edu and chengji@missouri.edu

genomics↗

GSDB: a database of 3D chromosome and genome structures reconstructed from Hi-C data

Advances in the study of chromosome conformation capture (3C) technologies, such as Hi-C technique - capable of capturing chromosomal interactions in a genome-wide scale - have led to the development of three-dimensional (3D) chromosome and genome structure reconstruction methods from Hi-C data. The 3D genome structure is important because it plays a role in a variety of important biological activities such as DNA replication, gene regulation, genome interaction, and gene expression. In recent years, numerous Hi-C datasets have been generated, and likewise, a number of genome structure construction algorithms have been developed. However, until now, there has been no freely available repository for 3D chromosome structures. In this work, we outline the construction of a novel Genome Structure Database (GSDB) to create a comprehensive repository that contains 3D structures for Hi-C datasets constructed by a variety of 3D structure reconstruction tools. GSDB contains over 50,000 structures constructed by 12 state-of-the-art chromosome and genome structure prediction methods for publicly used Hi-C datasets with varying resolution. The database is useful for the community to study the function of genome from a 3D perspective. GSDB is accessible at http://sysbio.rnet.missouri.edu/3dgenome/GSDB

bioinformatics↗