Lawson Gay (georgerat8)

Hi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https//yunliweb.its.unc.edu/FIREcaller.Single cell genomics offers an unprecedented resolution to interrogate genetic heterogeneity in a patient's tumour at the intercellular level. However, the DNA yield per cell is insufficient for today's sequencing library preparation protocols. This necessitates DNA amplification which is a key source of experimental noise. We provide an evaluation of two protocols using micro-fluidics based amplification for whole exome sequencing, which is an experimental scenario commonly used in single cell genomics. The results highlight their respective biases and relative strengths in identification of single nucleotide variations. Towards this end, we introduce a workflow SoVaTSiC, which allows for quality evaluation and somatic variant identification of single cell data. As proof of concept, the framework was applied to study a lung adenocarcinoma tumour. The analysis provides insights into tumour phylogeny by identifying key mutational events in lung adenocarcinoma evolution. The consequence of this inference is supported by the histology of the tumour and demonstrates usefulness of the approach.Ticks are arthropod ectoparasites and vectors of pathogens affecting human and animal health worldwide. The exoskeleton is a structure that protect arthropods from natural threats such as predators and diseases. Both structural proteins and chemical elements are components of the exoskeleton. However, the chemical composition and effect of pathogen infection on tick exoskeleton properties has not been characterized. In this study, we characterized the chemical composition of tick exoskeleton and the effect of Anaplasma pathogen infection on the chemical elements of the exoskeleton and selected structural proteins. The chemical composition was characterized ventral, dorsal upper and dorsal lower regions of tick exoskeleton by scanning electron microscopy and energy dispersive spectroscopy and compared between infected and uninfected ticks. The levels of selected structural proteins were analyzed in infected and uninfected I. scapularis salivary glands by immunofluorescence analysis. ABT-199 manufacturer The results showed that tick exoskeleton contains chemical elements also found in other arthropods. Some of the identified elements such as Mg and Al may be involved in tick exoskeleton stabilization through biomineralization of structural proteins that may be overrepresented in response to pathogen infection. These results suggested that pathogen infection alters the chemical composition of tick exoskeleton by mechanisms still to be characterized and with tick species and exoskeleton region-specific differences.Intestinal crypts are responsible for the total cell renewal of the lining of the intestines; this turnover is governed by the interplay between signalling pathways and the cell cycle. The role of Wnt signalling in cel