Bibliographic record
Abstract
Schizophrenia is a severe psychiatric disorder that affects approximately 1% of the general population. Childhood Onset Schizophrenia (COS) is a rare form of schizophrenia diagnosed during childhood (i.e. 6 to 13 years of age). The signs and symptoms of this early form of schizophrenia are continuous with those observed for adult schizophrenia and as such they equally impair the ability of those who are affected. Relatives who are genetically closer to a schizophrenic patient are more likely to develop the disorder themselves, and there is considerable interest in specific genetic mechanisms involved in its transmission. To this day the number of studies that examined the genetic risk associated to COS remains limited and only a few of those studies were focused on the identification of causative genes. With the advent of high-throughput sequencing instruments and whole exome capture arrays, genetic studies of schizophrenia recently tested the implication of de novo variants (variant not inherited from one of the two parents). The first chapter of this thesis describes an investigation of de novo variants across the entire coding regions (whole exome) of individuals diagnosed with COS. Our results showed such COS cases appear to present an increased number of missense variants that are predicted to have deleterious impact suggesting that de novo variants could represent an important aspect of the genetic architecture that underlies the development of COS. The following chapter describes a reexamination of the same whole exome sequencing (WES) data to identify inherited recessive variants. This analysis revealed an enrichment of disease related variants across the X-linked genes of male patients. Interestingly, human brain transcriptome data derived from the general population shows those X-linked genes are highly expressed in the brain. Overall these results represent the first published reports linking COS to single nucleotide variants identified using a tandem high throughput sequencing and genome wide approach (exome). The genes identified in our two studies represent a list of potential genetic risk factors linked to COS, which in turn provide clues about the pathogenicity of this complex disorder.
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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 | 0.001 | 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) | 0.006 | 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".