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Record W3029538724 · doi:10.1101/2020.05.26.115006

HIV Diversity Considerations in the Application of the Intact Proviral DNA Assay (IPDA)

2020· preprint· en· W3029538724 on OpenAlexaff
Natalie N. Kinloch, Yanqin Ren, Winiffer D. Conce Alberto, Winnie Dong, Pragya Khadka, Szu-Han Huang, Talia M. Mota, Andrew W. Wilson, Aniqa Shahid, Don Kirkby, Marianne Harris, Colin Kovacs, Erika Benko, Mario Ostrowski, Perla M. Del Río Estrada, Avery Wimpelberg, Christopher Cannon, William D. Hardy, Lynsay MacLaren, Harris Goldstein, Chanson J. Brumme, Guinevere Q. Lee, Rebecca M. Lynch, Zabrina L. Brumme, R. Brad Jones

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2020
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversity of TorontoUniversity of British ColumbiaAIDS VancouverMaple Leaf Medical ClinicSimon Fraser University
FundersNational Institute of Allergy and Infectious DiseasesNational Institute on Drug AbuseNational Institute of Mental HealthNational Heart, Lung, and Blood InstituteNational Institute on AgingNational Cancer InstituteNational Institutes of Health
KeywordsDigital polymerase chain reactionHuman immunodeficiency virus (HIV)Computational biologyBiologyDNAVirologyGeneticsGenePolymerase chain reaction

Abstract

fetched live from OpenAlex

Opening Paragraph (serves as abstract for submission) and Body The Intact Proviral DNA Assay (IPDA) was developed to address the critical need for a precise and scalable method for intact HIV reservoir quantification 1 . This duplexed droplet digital PCR (ddPCR) assay simultaneously targets the HIV Packaging Signal (Ψ) and the Rev Responsive Element (RRE) within Envelope ( env ) to distinguish genomically intact proviruses against a large background of defective ones 2 . The IPDA requires less time, resources, and biological material than the gold standard for replication-competent HIV reservoir measurement, the Quantitative Viral Outgrowth Assay (QVOA) 3 , and is being adopted in research and clinical studies 4–7 . In our cohort of HIV-1 subtype B-infected individuals from North America however, the IPDA yielded a 28% failure rate due to HIV polymorphism. We further demonstrate that within-host HIV diversity can lead the IPDA to underestimate intact HIV reservoir size, which could negatively impact clinical trial results interpretation. While the IPDA represents an important methodological advance, HIV diversity should be addressed before its widespread adoption.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.036
metaresearch head score (Gemma)0.055
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: none
Teacher disagreement score0.036
Threshold uncertainty score0.193

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0360.055
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.001
Science and technology studies0.0010.002
Scholarly communication0.0050.002
Open science0.0020.002
Research integrity0.0030.003
Insufficient payload (model declined to judge)0.0050.004

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 head0.021
GPT teacher head0.233
Teacher spread0.212 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreOther

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations16
Published2020
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicHIV Research and TreatmentFrench-language works237,207