Biology subjects

Tallon, L.

Publications and source records attributed to Tallon, L..

4 recordsLinked to original sources

bioRxiv2026

Rapid reduction in global chromatin loop size after acute STAG2 reconstitution in human cancer cells

Truncating mutations in the tumor suppressor STAG2, which encodes a component of the cohesin complex, are prevalent across diverse human cancers. Here, we report that acute reconstitution of physiological STAG2 levels in STAG2-mutant human glioblastoma multiforme cancer cells triggers a rapid reduction in the size of chromatin loops genome-wide. Despite this global change in chromatin loop size, early transcriptional responses to STAG2 restoration are limited to a small number of genes, most of which are induced by STAG2 reconstitution. Notably, the growth-suppressor EFEMP1 (Fibulin-3), a secreted glycoprotein that functions as an extracellular matrix-associated inhibitor of glioblastoma growth and invasion, was the only gene consistently induced across all experimental models. The most robust and conserved STAG2-induced genes all reside within intense chromatin loops whose anchors and overall intensity did not appear to change in response to STAG2 reconstitution. These findings suggest that inactivating mutations of STAG2 promote neoplastic transformation by alleviating a restriction on chromatin loop size, allowing for an expanded range of chromatin interactions that disrupts the maintenance of a tumor-suppressive transcriptome.

cancer biology↗

bioRxiv2023

High Coverage Highly Accurate Long-Read Sequencing of a Mouse Neuronal Cell Line Using the PacBio Revio Sequencer

Recently, Pacific Biosciences released a new highly accurate long-read sequencer called the Revio System that is projected to generate 30x HiFi whole-genome sequencing for the human genome within one sequencing SMRT Cell. Mouse and human genomes are similar in size. In this study, we sought to test this new sequencer by characterizing the genome and epigenome of the mouse neuronal cell line Neuro-2a. We generated long-read HiFi whole-genome sequencing on three Revio SMRT Cells, achieving a total coverage of 98x, with 30x, 32x, and 36x coverage respectively for each of the three Revio SMRT Cells. We performed several tests on these data including single-nucleotide variant and small insertion detection using GPU-accelerated DeepVariant, structural variant detection with pbsv, methylation detection with pb-CpG-tools, and generating de novo assemblies with the HiCanu and hifiasm assemblers. Overall, we find consistency across SMRT Cells in coverage, detection of variation, methylation, and de novo assemblies for each of the three SMRT Cells.

genomics↗

bioRxiv2020

Capture-based enrichment of Theileria parva DNA enables full genome assembly of first buffalo- derived strain and reveals exceptional intra-specific genetic diversity

Theileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle- and buffalo-associated T. parva populations. Here, we describe a capture-based target enrichment approach that enables, for the first time, de novo assembly of nearly complete T. parva genomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle- and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by [~]54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derived T. parva genome, which is larger than the genome from the reference, cattle-derived, Muguga strain. The average non-synonymous nucleotide diversity ({pi}N) per gene, between buffalo-derived T. parva and the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an average FST, genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle- and buffalo-derived T. parva parasites more commonly seen between, rather than within, species, with clear implications for vaccine development. The DNA capture approach used provides clear advantages over alternative T. parva DNA enrichment methods used previously and enables in-depth comparative genomics in this apicomplexan parasite.

genomics↗

bioRxiv2018

FDA-ARGOS: A Public Quality-Controlled Genome Database Resource for Infectious Disease Sequencing Diagnostics and Regulatory Science Research

Infectious disease next generation sequencing (ID-NGS) diagnostics are on the cusp of revolutionizing the clinical market. To facilitate this transition, FDA proactively invested in tools to support innovation of emerging technologies. FDA and collaborators established a publicly available database, FDA dAtabase for Regulatory-Grade micrObial Sequences (FDA-ARGOS), as a tool to fill reference database gaps with quality-controlled genomes. This manuscript discusses quality control metrics for the proposed FDA-ARGOS genomic resource and outlines the need for quality-controlled genome gap filling in the public domain. Here, we also present three case studies showcasing potential applications for FDA-ARGOS in infectious disease diagnostics, specifically: assay design, reference database and in silico sequence comparison in combination with representative microbial organism wet lab testing; a novel composite validation strategy for ID-NGS diagnostics. The use of FDA-ARGOS as an in silico comparator tool could reduce the burden for completing ID-NGS clinical trials. In addition, use cases identifying Enterococcus avium and Ebola virus (Zaire ebolavirus variant Makona) demonstrate the utility of FDA-ARGOS as a reference database for independent performance validation of new tests and for documenting how one would use this database as an in silico sequence target comparator tool for ID-NGS validation, respectively.

microbiology↗