Application of Whole Exome-trio Analysis Reveals Rare Variants Associated With Congenital Pouch Colon
Bibliographic record
Abstract
Abstract Anorectal malformations (ARMs) are individually common, but congenital pouch colon (CPC), a rare anorectal anomaly, causes a dilated pouch in the genitourinary tract. In this work, we attempted to identify de novo heterozygous missense variants and further discovered variants of unknown significance (VUS), which could provide insights into CPC manifestation and its etiology. From whole exome sequencing (WES) performed earlier, the trio exomes were analyzed from those who were admitted to J.K. Lon Hospital, SMS Medical College, Jaipur, India between 2011-2017. The proband exomes were compared with the unaffected sibling/family members, and we sought to ask whether any variants of significant interest are associated with the CPC manifestation. The WES data from a total of 64 samples, including 16 affected neonates with their parents and unaffected siblings, were used for the study. Although all samples had unaffected sibling samples and data, we restricted our pool of analyses to all probands (11 male and 5 female) and unaffected parents/siblings. We previously attempted to understand the genetic makeup of CPC and identified genes responsible for the disease using WES. We examined the role of rare allelic variation associated with CPC in a 16 proband/parent trio family comparing the mutations to those of their unaffected parents/siblings. Our study across 16 probands revealed extremely rare variants, viz. TAF1B, MUC5B and FRG1. The variants were further validated to reveal disease-causing mutations associated with CPC and genitourinary diseases that could close the gaps of surgery by bringing intervention in therapies.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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".