Publications associées à CRISPR-Cas9-mediated saturated mutagenesis screen predicts clinical drug resistance with improved accuracy

The role of LRRK2 in lung adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths worldwide and the most common lung cancer subtype is lung adenocarcinoma (LUAD). Frequently mutated genes involve activating mutations in KRAS and loss of function mutations in TP53. LUADs primarily ...

EPFL2024

Single-mitosis dissection of acute and chronic DNA mutagenesis and repair

Christina Ernst

How chronic mutational processes and punctuated bursts of DNA damage drive evolution of the cancer genome is poorly understood. Here, we demonstrate a strategy to disentangle and quantify distinct mechanisms underlying genome evolution in single cells, dur ...

Nature Portfolio2024

Mutation-Attention (MuAt): deep representation learning of somatic mutations for tumour typing and subtyping

Sebastian Martin Waszak

Background: Cancer genome sequencing enables accurate classification of tumours and tumour subtypes. However, prediction performance is still limited using exome-only sequencing and for tumour types with low somatic mutation burden such as many paediatri ...

2023

Whole-genome doubling drives oncogenic loss of chromatin segregation

Elisa Oricchio, Natalya Katanayeva, Ruxandra-Andreea Lambuta, Juan Diaz Miyar, Giovanni Ciriello, Daniele Tavernari

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies(1-8). However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotyp ...

NATURE PORTFOLIO2023

The role of the NF-kappaB pathway in Amyotrophic lateral sclerosis pathogenesis

Emma Charlotta Källstig

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor disorder, which results in death within a few years of diagnosis. While the cause of most cases of ALS is unknown, 10% of cases are familial (fALS), and associated with mutations in one of ov ...

EPFL2023

Disentangle genus microdiversity within a complex microbial community by using a multi-distance long-read binning method: example of Candidatus Accumulibacter

Aline Sondra Adler, Christof Holliger, Julien Maillard, Marco Pagni, Simon Marius Jean Poirier

Complete genomes can be recovered from metagenomes by assembling and binning DNA sequences into metagenome assembled genomes (MAGs). Yet, the presence of microdiversity can hamper the assembly and binning processes, possibly yielding chimeric, highly fragm ...

WILEY2022

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

Integrative transcriptome analyses of Transposable Elements (TEs) and genes contribute to a better understanding of colorectal cancer

Eunji Shin

Cancer is the second leading cause of death worldwide. Cancer develops through multiple hallmark functions including apoptosis evasion, unlimited replicative potential, metastasis, and immune avoidance. Over the past few decades, researchers have reported ...

EPFL2022

Allosteric control of type I-A CRISPR-Cas3 complexes and establishment as effective nucleic acid detection and human genome editing tools

Henning Paul-Julius Stahlberg, Dongchun Ni

Type I CRISPR-Cas systems typically rely on a two-step process to degrade DNA. First, an RNA-guided complex named Cascade identifies the complementary DNA target. The helicase-nuclease fusion enzyme Cas3 is then recruited in trans for processive DNA degrad ...

CELL PRESS2022

Interferon Lambda Delays the Emergence of Influenza Virus Resistance to Oseltamivir

Francesco Stellacci, Paulo Henrique Jacob Silva, Chiara Medaglia

Influenza viruses are a leading cause of morbidity and mortality worldwide. These air-borne pathogens are able to cross the species barrier, leading to regular seasonal epidemics and sporadic pandemics. Influenza viruses also possess a high genetic variabi ...

2021

Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1(T315I) and BCR-ABL1(T315I-E255K)

Oliver Hantschel

Resistance remains the major clinical challenge for the therapy of Philadelphia chromosome-positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common "gatekeeper" mutation T315I ...

SPRINGER2021

Somatic Mitochondrial DNA Point Mutations Used as Biomarkers to Demonstrate Genomic Heterogeneity in Primary Prostate Cancer

Paul Refinetti, Per Olaf Ekstrom

Primary prostate tumor heterogeneity is poorly understood, leaving research efforts with challenges regarding the initiation and advancement of the disease. The growth of tumor cells is accompanied by mutations in nuclear and in mitochondrial genomes. Thus ...

HINDAWI LTD2020

Trametinib Induces the Stabilization of a Dual GNAQ p.Gly48Leu-and FGFR4 p.Cys172Gly-Mutated Uveal Melanoma. The Role of Molecular Modelling in Personalized Oncology

Olivier Michielin, Alexandre Wicky, Krisztian Homicsko

We report a case of an uveal melanoma patient with GNAQ p.Gly48Leu who responded to MEK inhibition. At the time of the molecular analysis, the pathogenicity of the mutation was unknown. A tridimensional structural analysis showed that G alpha(q) can adopt ...

2020

Notch Signaling - a Booster of Chronic Lymphocytic Leukemia During Initiation and Disease Progression

Delphine Maude Tardivon

Chronic lymphocytic leukemia (CLL) is a B cell malignancy and represents the most common leukemia in adults within the Western world. This disease mainly affects the elderly, with a median age of diagnosis over 70. The disease course is highly variable amo ...

EPFL2020

Rapid Screen for Tyrosine Kinase Inhibitor Resistance Mutations and Substrate Specificity

Oliver Hantschel, Sandrine Madeleine Suzanne Georgeon, Sina Maren Reckel

We present a rapid and high-throughput yeast and flow cytometry based method for predicting kinase inhibitor resistance mutations and determining kinase peptide substrate specificity. Despite the widespread success of targeted kinase inhibitors as cancer t ...

AMER CHEMICAL SOC2019

Directed evolution of the optoelectronic properties of synthetic nanomaterials

Ardemis Anoush Boghossian, Shang-Jung Wu, Benjamin Paul Johanès Gabriel Lambert, Alice Judith Gillen

Directed evolution is a powerful approach to tailor protein properties toward new or enhanced functions. Herein, we use directed evolution to engineer the optoelectronic properties of DNA-wrapped single-walled carbon nanotube sensors through DNA mutation. ...

Royal Society of Chemistry2019

Predicting the Occurrence of Variants in RAG1 and RAG2

Jacques Fellay, Flavia Aurelia Shoko Hodel, Dylan Lawless

While widespread genome sequencing ushers in a new era of preventive medicine, the tools for predictive genomics are still lacking. Time and resource limitations mean that human diseases remain uncharacterized because of an inability to predict clinically ...

2019

Analysis of Inherited Optic Neuropathies

Background Inherited optic neuropathies (IONs) cover a spectrum of clinically and genetically heterogenic conditions. Genetic evaluation of patients with IONs may enable their better clinico-diagnostic assessment and management of the disease. The aim of t ...

2019

Method for Identification of Threonine Isoforms in Peptides by Ultraviolet Photofragmentation of Cold Ions

Oleg Boyarkine, Vladimir Kopysov, Aleksandr Pereverzev, Elizaveta Solovyeva

Identification of isomeric amino acid residues in peptides and proteins is challenging but often highly desired in proteomics. One of the practically important cases that require isomeric assignments is that associated with single-nucleotide polymorphism s ...

AMER CHEMICAL SOC2019

ZNF445 is a primary regulator of genomic imprinting

Didier Trono, Priscilla Turelli, Sandra Eloise Kjeldsen, Michaël Imbeault, Andrea Coluccio, Evaristo Jose Planet Letschert, Christian Axel Wandall Thorball

Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertil ...

2019