Going with the flow of autophagy in Crohnʼs disease: IRGM risk polymorphism found upstream
Bibliographic record
Abstract
McCarroll SA, Huett A, Kuballa P, et al. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nat Genet. 2008;40:1107–1112. Recent genome-wide association (GWA) and replication studies have implicated the autophagy genes ATG16L1 and IRGM genes as susceptibility genes for, in particular, Crohn's disease (CD). For the IRGM gene1, 2 the association signal resided upstream of the 5′ end of the gene. Efforts to identify potential causal variants in the coding regions of the gene had not been successful, as the identified variants were of low frequency and were not associated with CD risk. In order to further dissect the reported association between IRGM and CD, McCarroll et al3 extensively investigated the putative genomic region corresponding to the 5′ upstream region of IRGM. As initial efforts to genotype the segment in 34 HapMap samples resulted in numerous null genotypes, they postulated that the region may harbor “structural variations.” To confirm this, they analyzed 270 HapMap samples using a hybrid array of single nucleotide polymorphism (SNP) and copy-number probes (SNP6.0 array). Observations that 6 copy-number probes spanning a 13 –kb region near IRGM showed correlated variation in intensity scores across samples provided further evidence for the presence of a common copy-number polymorphism in the region. Follow-up quantitative polymerase chain reaction (qPCR) assays indicated that the polymorphism was an insertion-deletion in perfect linkage disequilibrium (LD) with the GWA-identified lead SNP rs13361189. PCR capture and sequencing in 6 individuals demonstrated that the polymorphism led to the removal of 20,103 nucleotides that were replaced with 7 nucleotides.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.008 | 0.005 |
| Insufficient payload (model declined to judge) | 0.004 | 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".