Functional analysis and structural modeling of human APOBEC3G reveal the role of evolutionarily conserved elements in the inhibition of human immunodeficiency virus type 1 infection and Alu transposition

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Wide-scale identification of novel/eliminated genes responsible for evolutionary transformations

Daria Korotkova

BackgroundIt is generally accepted that most evolutionary transformations at the phenotype level are associated either with rearrangements of genomic regulatory elements, which control the activity of gene networks, or with changes in the amino acid conten ...

2023

cgNA+: A sequence-dependent coarse-grain model of double-stranded nucleic acids

Rahul Sharma

DNA mechanics plays a crucial role in many biological processes, including nucleosome positioning and protein-DNA interactions. It is believed that nature employs epigenetic modifications in DNA to further regulate gene expression. Moreover, double-strande ...

EPFL2023

Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years

Jacques Fellay, Christian Axel Wandall Thorball

Background Accelerated epigenetic ageing can occur in untreated HIV infection and is partially reversible with effective antiretroviral therapy (ART). We aimed to make a long-term comparison of epigenetic ageing dynamics in people with HIV during untreated ...

ELSEVIER2023

Landscapes of DNA Mechanics and Genomes

Thomas Antonin Zwahlen

The local physical properties - such as shape and flexibility - of the DNA double-helix is today widely believed to be influenced by nucleic acid sequence in a non-trivial way. Furthermore, there is strong evidence that these properties play a role in many ...

EPFL2023

Phylogenetic estimation of the viral fitness landscape of HIV-1 set-point viral load

Jacques Fellay

Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical opti ...

OXFORD UNIV PRESS2022

Extracting phylogenetic dimensions of coevolution reveals hidden functional signals

Anne-Florence Raphaëlle Bitbol

Despite the structural and functional information contained in the statistical coupling between pairs of residues in a protein, coevolution associated with function is often obscured by artifactual signals such as genetic drift, which shapes a protein's ph ...

Nature Portfolio2022

Transposon-activated POU5F1B promotes colorectal cancer growth and metastasis

Didier Trono, Laurence Gouzi Abrami, Julien Léonard Duc, Sandra Eloise Kjeldsen, Evaristo Jose Planet Letschert, Alexandre Coudray, Laia Simo Riudalbas, Sagane Dind

The treatment of colorectal cancer (CRC) is an unmet medical need in absence of early diagnosis. Here, upon characterizing cancer-specific transposable element-driven transpochimeric gene transcripts (TcGTs) produced by this tumor in the SYSCOL cohort, we ...

Nature Research2022

Protein language models trained on multiple sequence alignments learn phylogenetic relationships

Anne-Florence Raphaëlle Bitbol, Damiano Sgarbossa, Umberto Lupo

Self-supervised neural language models with attention have recently been applied to biological sequence data, advancing structure, function and mutational effect prediction. Some protein language models, including MSA Transformer and AlphaFold's EvoFormer, ...

Nature Portfolio2022

Dynamics of the most common pathogenic mtDNA variant m.3243A > G demonstrate frequency-dependency in blood and positive selection in the germline

Konstantin Popadin

The A-to-G point mutation at position 3243 in the human mitochondrial genome (m.3243A > G) is the most common pathogenic mtDNA variant responsible for disease in humans. It is widely accepted that m.3243A > G levels decrease in blood with age, and an age c ...

Oxford University Press2022

A Baseline Cellular Antiviral State Is Maintained by cGAS and Its Most Frequent Naturally Occurring Variant rs610913

Jacques Fellay, Christian Axel Wandall Thorball

Upon recognition of aberrantly located DNA, the innate immune sensor cyclic GMP-AMP synthase (cGAS) activates stimulator of IFN genes (STING)/IFN regulatory factor (IRF)3-driven antiviral responses. In this study, we characterized the ability of a specific ...

American Association of Immunologists ; Oxford University Press2022