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Record W2170066264 · doi:10.7554/elife.01123

A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

2013· article· en· W2170066264 on OpenAlex
István Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. McLaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martínez‐Picado, Judith Dalmau, Cecilio López‐Galíndez, Concha Casado, Andri Rauch, Huldrych F. Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O’Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolò Fusi, Zoltán Kutalik, Todd M. Allen, Viktor Müller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueeLife · 2013
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversity of British ColumbiaAIDS VancouverSimon Fraser University
FundersNational Cancer InstituteMinisterio de Ciencia e InnovaciónMagyar Tudományos AkadémiaCanadian Institutes of Health ResearchEidgenössische Technische Hochschule ZürichSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungMichael Smith Health Research BCNational Institute of Allergy and Infectious DiseasesBill and Melinda Gates Foundation
KeywordsGenomeBiologyGenetic variationGeneticsHuman genomeHuman genetic variationGenetic diversityHuman immunodeficiency virus (HIV)Computational biologyEvolutionary biologySequence (biology)Diversity (politics)VirologyGenePopulationMedicine

Abstract

fetched live from OpenAlex

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the 'intermediate phenotype' nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host-pathogen interaction. DOI:http://dx.doi.org/10.7554/eLife.01123.001.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.121
Threshold uncertainty score0.782

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.265
Teacher spread0.242 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it