Publications de Paul Jack Mc Laren

HIV peptidome-wide association study reveals patient-specific epitope repertoires associated with HIV control

Jacques Fellay, Paul Jack Mc Laren, Nimisha Chaturvedi

Genetic variation in the peptide-binding groove of the highly polymorphic HLA class I molecules has repeatedly been associated with HIV-1 control and progression to AIDS, accounting for up to 12% of the variation in HIV-1 set point viral load (spVL). This ...

National Academy of Sciences2019

Severe viral respiratory infections in children with IFIH1 loss-of-function mutations

Thomas Junier, Amalio Telenti, Samira Asgari, Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren, Christian Hammer

Viral respiratory infections are usually mild and self-limiting; still they exceptionally result in life-threatening infections in previously healthy children. To investigate a potential genetic cause, we recruited 120 previously healthy children requiring ...

Natl Acad Sciences2017

No Evidence for Association of beta-Defensin Genomic Copy Number with HIV Susceptibility, HIV Load during Clinical Latency, or Progression to AIDS

Jacques Fellay, Paul Jack Mc Laren

Common single-nucleotide variation in the host accounts for 25% of the variability in the plasma levels of HIV during the clinical latency stage (viral load set point). However, the role of rare variants and copy number variants remains relatively unexplor ...

Wiley-Blackwell2017

Estimating the Respective Contributions of Human and Viral Genetic Variation to HIV Control

Amalio Telenti, Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren

We evaluated the fraction of variation in HIV-1 set point viral load attributable to viral or human genetic factors by using joint host/pathogen genetic data from 541 HIV infected individuals. We show that viral genetic diversity explains 29% of the variat ...

Public Library of Science2017

Evaluating the Impact of Functional Genetic Variation on HIV-1 Control

Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren

Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. ...

Oxford Univ Press Inc2017

Method for privacy-preserving medical risk test

Jean-Pierre Hubaux, Amalio Telenti, Erman Ayday, Paul Jack Mc Laren, Jean Louis Raisaro

A privacy-preserving method for performing a disease susceptibility test on a patient, said method comprising: (I) performing homomorphic computations, (J) obtaining a test result which is partly decrypted with a first part (prk1 resp. prk2) of a private k ...

2016

Exome Sequencing Reveals Primary Immunodeficiencies in Children with Community-Acquired Pseudomonas aeruginosa Sepsis

Christoph Berger, Richard Wong, Samira Asgari, Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren

One out of three pediatric sepsis deaths in high income countries occur in previously healthy children. Primary immunodeficiencies (PIDs) have been postulated to underlie fulminant sepsis, but this concept remains to be confirmed in clinical practice. Pseu ...

Frontiers Media Sa2016

Privacy-preserving genomic testing in the clinic: a model using HIV treatment

Jean-Pierre Hubaux, Amalio Telenti, Jacques Fellay, Erman Ayday, Istvan Bartha, Paul Jack Mc Laren, Jean Louis Raisaro

The implementation of genomic-based medicine is hindered by unresolved questions regarding data privacy and delivery of interpreted results to health-care practitioners. We used DNA-based prediction of HIV-related outcomes as a model to explore critical is ...

Nature Publishing Group2016

Corrigendum: Exome Sequencing reveals Primary immunodeficiencies in Children with Community-Acquired Pseudomonas aeruginosa Sepsis (vol 7, 357, 2016)

Christoph Berger, Richard Wong, Samira Asgari, Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren

Frontiers Media Sa2016

Identification of Siglec-1 null individuals infected with HIV-1

Amalio Telenti, Jacques Fellay, Paul Jack Mc Laren

Siglec-1/CD169 is a myeloid-cell surface receptor critical for HIV-1 capture and infection of bystander target cells. To dissect the role of SIGLEC1 in natura, we scan a large population genetic database and identify a loss-of-function variant (Glu88Ter) t ...

Nature Publishing Group2016

Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses

Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren, Christian Hammer

The magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,36 ...

Cell Press2015

Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols

Paul Jack Mc Laren

Background Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containi ...

Lippincott Williams & Wilkins2015

The Characteristics of Heterozygous Protein Truncating Variants in the Human Genome

Amalio Telenti, Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren, Nimisha Chaturvedi

Sequencing projects have identified large numbers of rare stop-gain and frameshift variants in the human genome. As most of these are observed in the heterozygous state, they test a gene's tolerance to haploinsufficiency and dominant loss of function. We a ...

Public Library Science2015

Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses

Amalio Telenti, Jérémie Perreaud, Danielle Thompson, Paul Jack Mc Laren, Daniel Sauter

Background: Known antiretroviral restriction factors are encoded by genes that are under positive selection pressure, induced during HIV-1 infection, up-regulated by interferons, and/or interact with viral proteins. To identify potential novel restriction ...

Biomed Central Ltd2015

Human genetic variation in HIV disease: beyond genome-wide association studies

Jacques Fellay, Paul Jack Mc Laren

PURPOSE OF REVIEW: Rapid expansion of genomic technologies has resulted in an unprecedented ability to interrogate the impact of human genetic variation on disease. HIV-1 infection is a unique model for studying this impact because host genetic variation i ...

Lippincott Williams & Wilkins2015

The impact of host genetic variation on infection with HIV-1

Paul Jack Mc Laren

The outcome after infection with the human immunodeficiency virus type 1 (HIV-1) is a complex phenotype determined by interactions among the pathogen, the human host and the surrounding environment. An impact of host genetic variation on HIV-1 susceptibili ...

Nature Publishing Group2015

Polymorphisms of large effect explain the majority of the host genetic contribution to variation of HIV-1 virus load

Amalio Telenti, Jacques Fellay, Istvan Bartha, Paul Jack Mc Laren

Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. ...

National Academy of Sciences2015

A Novel Acute Retroviral Syndrome Severity Score Predicts the Key Surrogate Markers for HIV-1 Disease Progression

Jacques Fellay, Paul Jack Mc Laren

Objective: Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest ris ...

Public Library of Science2014

Disentangling human tolerance and resistance against HIV

Amalio Telenti, Jacques Fellay, Paul Jack Mc Laren

In ecology, "disease tolerance" is defined as an evolutionary strategy of hosts against pathogens, characterized by reduced or absent pathogenesis despite high pathogen load. To our knowledge, tolerance has to date not been quantified and disentangled from ...

Public Library Science2014

HLA class I and KIR genes do not protect against HIV type 1 infection in highly exposed uninfected individuals with hemophilia A

Jacques Fellay, Paul Jack Mc Laren

A recent genome-wide association study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with human immunodeficiency virus type 1 (HIV-1) did not reveal genetic variants associated with resistance to HIV-1 infection, beyond hom ...

Oxford University Press2014