HLA-associated viral polymorphism in chronically HIV-1-infected Japanese cohort: analysis of four-digit HLA allele level
Bibliographic record
Abstract
It is assumed that the difference of HLA class I distribution among ethnic populations influences HIV evolution because HLA-restricted immune pressure selects escape mutations. Approximately 50% of HLA class I alleles are shared between Japanese and Caucasians. The analysis of HLA-associated polymorphism (HLA-AP) in both Japanese and Caucasian infected with clade B virus is expected to clarify the difference of HIV-1 evolution between both populations. We sequenced Gag, Pol, and Nef genes in 430 treatment-naïve Japanese chronically infected with HIV-1 clade B and then identified HLA-associated amino acids at each codon using a phylogenetically corrected logistic regression model and false discovery rates to correct for multiple tests. We completely determined 400, 366, and 309 sequences of Gag, Pol, and Nef, respectively, and then analyzed polymorphisms associated with 78 four-digit HLA alleles (21 HLA-A, 38 HLA-B, and 19 HLA-C alleles). At the threshold of q<0.2, we found 195 HLA-APs (67 in Gag, 61 in Pol, and 67 in Nef). These polymorphisms were observed at 39 of 501 (7.8%) Gag, 42 of 1004 (4.2%) Pol, and 33 of 207 (16.0%) Nef codons. Ninety-six HLA-APs associated with more than one HLA subtype allele were detected in 4-digital HLA allele analysis. Approximately 40% of HLA-APs were associated with HLA alleles predominantly found in Asia. Out of HLA-APs associated with common HLA alleles, approximately 50% were found in Caucasian population (IHAC cohort). This study demonstrated that only 30% of HLA-APs were shared between Caucasians and Japanese, indicating that the difference in HLA allele distributions resulted in distinct HIV-1 evolution.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
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".