A nucleosome switch primes Hepatitis B Virus infection

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Summary:

Chronic hepatitis B virus (HBV) infection is an incurable global health threat responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, Smc5/6. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. Establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA drives X transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing molecule CBL137 inhibits X transcription and HBV infection in hepatocytes. Our results shed light on a long-standing paradox and represent a potential new therapeutic avenue for the treatment of chronic HBV infection.

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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Michael Love, Wolfgang Huber, Simon Anders (2014)

In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.

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Fast gapped-read alignment with Bowtie 2.

Ben Langmead, Steven L Salzberg (2022)

As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.

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BEDTools: a flexible suite of utilities for comparing genomic features

Aaron Quinlan, Ira Hall (2010)

Motivation: Testing for correlations between different sets of genomic features is a fundamental task in genomics research. However, searching for overlaps between features with existing web-based methods is complicated by the massive datasets that are routinely produced with current sequencing technologies. Fast and flexible tools are therefore required to ask complex questions of these data in an efficient manner. Results: This article introduces a new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format. BEDTools also supports the comparison of sequence alignments in BAM format to both BED and GFF features. The tools are extremely efficient and allow the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks. BEDTools can be combined with one another as well as with standard UNIX commands, thus facilitating routine genomics tasks as well as pipelines that can quickly answer intricate questions of large genomic datasets. Availability and implementation: BEDTools was written in C++. Source code and a comprehensive user manual are freely available at http://code.google.com/p/bedtools Contact: aaronquinlan@gmail.com; imh4y@virginia.edu Supplementary information: Supplementary data are available at Bioinformatics online.

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Author and article information

Contributors

Nicholas A. Prescott:

ORCID: http://orcid.org/0000-0002-0635-8906

Role: ConceptualizationRole: MethodologyRole: InvestigationRole: VisualizationRole: Writing – Original DraftRole: Writing – Review & EditingRole: Project AdministrationRole: Funding acquisition

Andrés Mansisidor:

ORCID: http://orcid.org/0000-0002-6607-4016

Role: MethodologyRole: InvestigationRole: VisualizationRole: Writing – Review & EditingRole: Funding acquisition

Yaron Bram:

ORCID: http://orcid.org/0000-0001-9711-575X

Role: MethodologyRole: InvestigationRole: Writing – Review & Editing

Tracy Biaco: Role: MethodologyRole: InvestigationRole: Writing – Review & Editing

Justin Rendleman:

ORCID: http://orcid.org/0000-0001-8152-7127

Role: InvestigationRole: VisualizationRole: Writing – Review & Editing

Sarah C. Faulkner:

ORCID: http://orcid.org/0000-0002-6085-7423

Role: MethodologyRole: InvestigationRole: Writing – Review & Editing

Abigail A. Lemmon:

ORCID: http://orcid.org/0000-0001-6798-9384

Role: InvestigationRole: Writing – Review & Editing

Christine Lim: Role: Investigation

Pierre-Jacques Hamard:

ORCID: http://orcid.org/0000-0002-2484-6161

Role: Investigation

Richard P. Koche:

ORCID: http://orcid.org/0000-0002-6820-5083

Role: Investigation

Viviana I. Risca:

ORCID: http://orcid.org/0000-0003-2670-8704

Role: MethodologyRole: InvestigationRole: Writing – Review & EditingRole: SupervisionRole: Project AdministrationRole: Funding acquisition

Robert E. Schwartz:

ORCID: http://orcid.org/0000-0002-5417-5995

Role: ConceptualizationRole: Writing – Review & EditingRole: SupervisionRole: Project AdministrationRole: Funding acquisition

Yael David:

ORCID: http://orcid.org/0000-0003-1696-0025

Role: ConceptualizationRole: Writing – Original DraftRole: Writing – Review & EditingRole: SupervisionRole: Project AdministrationRole: Funding acquisition

Journal

Journal ID (nlm-ta): bioRxiv

Journal ID (publisher-id): BIORXIV

Title: bioRxiv

Publisher: Cold Spring Harbor Laboratory

ISSN (Electronic): 2692-8205

Publication date (Electronic): 12 June 2024

Electronic Location Identifier: 2023.03.03.531011

Affiliations

[1 ]Tri-Institutional PhD Program in Chemical Biology; New York, NY 10065, USA

[2 ]Chemical Biology Program, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA

[3 ]Laboratory of Genome Architecture and Dynamics, The Rockefeller University; New York, NY 10065, USA

[4 ]Division of Gastroenterology & Hepatology, Department of Medicine, Weill Cornell Medicine; New York, NY 10065, USA

[5 ]Department of Pharmacology, Weill Cornell Medicine; New York, NY 10065, USA

[6 ]Epigenetics Research Innovation Lab, Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center; New York, NY 10065, USA

[7 ]Department of Physiology and Biophysics, Weill Cornell Medicine; New York, NY 10065, USA

[8 ]These authors contributed equally

[9 ]Lead Contact

Author notes

[* ]Correspondence: res2025@ 123456med.cornell.edu (R.E.S.), davidshy@ 123456mskcc.org (Y.D.)

Author information

Nicholas A. Prescott http://orcid.org/0000-0002-0635-8906

Andrés Mansisidor http://orcid.org/0000-0002-6607-4016

Yaron Bram http://orcid.org/0000-0001-9711-575X

Justin Rendleman http://orcid.org/0000-0001-8152-7127

Sarah C. Faulkner http://orcid.org/0000-0002-6085-7423

Abigail A. Lemmon http://orcid.org/0000-0001-6798-9384

Pierre-Jacques Hamard http://orcid.org/0000-0002-2484-6161

Richard P. Koche http://orcid.org/0000-0002-6820-5083

Viviana I. Risca http://orcid.org/0000-0003-2670-8704

Robert E. Schwartz http://orcid.org/0000-0002-5417-5995

Yael David http://orcid.org/0000-0003-1696-0025

Article

DOI: 10.1101/2023.03.03.531011

PMC ID: 11195122

PubMed ID: 38915612

SO-VID: c35c2a0e-f3cc-4d7b-9d0c-1672363e1424

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This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.

A nucleosome switch primes Hepatitis B Virus infection

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Point-Of-Care Testing for Hepatitis

Most cited references 94

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Fast gapped-read alignment with Bowtie 2.

BEDTools: a flexible suite of utilities for comparing genomic features

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