Biology subjects

Min, A.

Publications and source records attributed to Min, A..

5 recordsLinked to original sources

bioRxiv2024

Predicting chromatin conformation contact maps

Over the past 15 years, a variety of next-generation sequencing assays have been developed for measuring the 3D conformation of DNA in the nucleus. Each of these assays gives, for a particular cell or tissue type, a distinct picture of 3D chromatin architecture. Accordingly, making sense of the relationship between genome structure and function requires teasing apart two closely related questions: how does chromatin 3D structure change from one cell type to the next, and how do different measurements of that structure differ from one another, even when the two assays are carried out in the same cell type? In this work, we assemble a collection of chromatin 3D datasets--each represented as a 2D contact map-- spanning multiple assay types and cell types. We then build a machine learning model that predicts missing contact maps in this collection. We use the model to systematically explore how genome 3D architecture changes, at the level of compartments, domains, and loops, between cell type and between assay types.

bioinformatics↗

bioRxiv2022

Matrix prior for data transfer between single cell data types in latent Dirichlet allocation

Single cell ATAC-seq (scATAC-seq) enables the mapping of regulatory elements in fine-grained cell types. Despite this advance, analysis of the resulting data is challenging, and large scale scATAC-seq data are difficult to obtain and expensive to generate. This motivates a method to leverage information from previously generated large scale scATAC-seq or scRNA-seq data to guide our analysis of new scATAC-seq datasets. We analyze scATAC-seq data using latent Dirichlet allocation (LDA), a Bayesian algorithm that was developed to model text corpora, summarizing documents as mixtures of topics defined based on the words that distinguish the documents. When applied to scATAC-seq, LDA treats cells as documents and their accessible sites as words, identifying "topics" based on the cell type-specific accessible sites in those cells. Previous work used uniform symmetric priors in LDA, but we hypothesized that nonuniform matrix priors generated from LDA models trained on existing data sets may enable improved detection of cell types in new data sets, especially if they have relatively few cells. In this work, we test this hypothesis in scATAC-seq data from whole C. elegans nematodes and SHARE-seq data from mouse skin cells. We show that nonsymmetric matrix priors for LDA improve our ability to capture cell type information from small scATAC-seq datasets.

bioinformatics↗

bioRxiv2021

Comparing Heritability Estimators under Alternative Structures of Linkage Disequilibrium

SNP heritability of a trait is the proportion of its variance explained by the additive effects of the genome-wide single nucleotide polymorphisms (SNPs). The existing approaches to estimate SNP heritability can be broadly classified into two categories. One set of approaches model the SNP effects as fixed effects and the other treats the SNP effects as random effects. These methods make certain assumptions about the dependency among individuals (familial relationship) as well as the dependency among markers (linkage disequilibrium, LD) to provide consistent estimates of SNP heritability as the number of individuals increases. While various approaches have been proposed to account for such dependencies, it remains unclear which estimates reported in the literature are more robust against various model mis-specifications. Here we investigate the impact of different structures of LD and familial relatedness on heritability estimation. We show that the performance of different methods for heritability estimation depends heavily on the structure of the underlying pattern of LD and the degree of relatedness among sampled individuals. However, contrary to the claim in the current literature, we did not find significant differences in the performance of these fixed-SNP-effects and random-SNP-effects approaches. Moreover, we established the equivalence between the two method-of-moments estimators, one from each of these two lines of approaches.

genetics↗

bioRxiv2020

Novel Cluster AZ Arthrobacter phages Powerpuff, Lego, and YesChef exhibit close functional relationships with Microbacterium phages

Bacteriophages exhibit a vast spectrum of relatedness and there is increasing evidence of close genomic relationships independent of host genus. The variability in phage similarity at the nucleotide, amino acid, and gene content levels confounds attempts at quantifying phage relatedness, especially as more novel phages are isolated. This study describes three highly similar novel Arthrobacter globiformis phages-Powerpuff, Lego, and YesChef-which were assigned to Cluster AZ using a nucleotide-based clustering parameter. Phages in Cluster AZ and Microbacterium Cluster EH, as well as the former Microbacterium singleton Zeta1847, exhibited low nucleotide similarity but gene content similarity in excess of the recently adopted Microbacterium clustering parameter, which resulted in the reassignment of Zeta1847 to Cluster EH. Additionally, Clusters AZ and EH phages encode a shared integrase indicative of a lysogenic life cycle; in the first experimental verification of a Cluster AZ phages life cycle, we show that phage Powerpuff is a true temperate phage and forms stable lysogens that exhibit immunity to superinfection by related phages, despite lacking identifiable repressors typically required for lysogenic maintenance and superinfection immunity. The ability of phage Powerpuff to undergo and maintain lysogeny suggests that other closely related phages encoding an integrase but lacking an identified repressor may be temperate as well. Our findings further highlight the importance of using multiple metrics to capture phage relatedness, provide additional evidence of significant shared phage genomic content spanning multiple actinobacterial host genera, and demonstrate the continued need for verification and characterization of life cycles in newly isolated phages.

microbiology↗

bioRxiv2019

CoralP: Flexible visualization of the human phosphatome

Protein phosphatases and kinases play critical roles in a host of biological processes and diseases via the removal and addition of phosphoryl groups. While kinases have been extensively studied for decades, recent findings regarding the specificity and activities of phosphatases have generated an increased interest in targeting phosphatases for pharmaceutical development. This increased focus has created a need for methods to visualize this important class of proteins within the context of the entire phosphatase protein family. Here, we present CoralP, an interactive web application for the generation of customizable, publication-quality representations of human phosphatome data. Phosphatase attributes can be encoded through edge colors, node colors, and node sizes. CoralP is the first and currently the only tool designed for phosphatome visualization and should be of great use to the signaling community. The source code and web application are available at https://github.com/PhanstielLab/coralp and http://phanstiel-lab.med.unc.edu/coralp respectively.

bioinformatics↗