Diagnosis of a Single-Nucleotide Variant in Whole-Exome Sequencing Data for Patients With Inherited Diseases: Machine Learning Study Using Artificial Intelligence Variant Prioritization
Notice bibliographique
Résumé
BACKGROUND: In recent years, thanks to the rapid development of next-generation sequencing (NGS) technology, an entire human genome can be sequenced in a short period. As a result, NGS technology is now being widely introduced into clinical diagnosis practice, especially for diagnosis of hereditary disorders. Although the exome data of single-nucleotide variant (SNV) can be generated using these approaches, processing the DNA sequence data of a patient requires multiple tools and complex bioinformatics pipelines. OBJECTIVE: This study aims to assist physicians to automatically interpret the genetic variation information generated by NGS in a short period. To determine the true causal variants of a patient with genetic disease, currently, physicians often need to view numerous features on every variant manually and search for literature in different databases to understand the effect of genetic variation. METHODS: We constructed a machine learning model for predicting disease-causing variants in exome data. We collected sequencing data from whole-exome sequencing (WES) and gene panel as training set, and then integrated variant annotations from multiple genetic databases for model training. The model built ranked SNVs and output the most possible disease-causing candidates. For model testing, we collected WES data from 108 patients with rare genetic disorders in National Taiwan University Hospital. We applied sequencing data and phenotypic information automatically extracted by a keyword extraction tool from patient's electronic medical records into our machine learning model. RESULTS: We succeeded in locating 92.5% (124/134) of the causative variant in the top 10 ranking list among an average of 741 candidate variants per person after filtering. AI Variant Prioritizer was able to assign the target gene to the top rank for around 61.1% (66/108) of the patients, followed by Variant Prioritizer, which assigned it for 44.4% (48/108) of the patients. The cumulative rank result revealed that our AI Variant Prioritizer has the highest accuracy at ranks 1, 5, 10, and 20. It also shows that AI Variant Prioritizer presents better performance than other tools. After adopting the Human Phenotype Ontology (HPO) terms by looking up the databases, the top 10 ranking list can be increased to 93.5% (101/108). CONCLUSIONS: We successfully applied sequencing data from WES and free-text phenotypic information of patient's disease automatically extracted by the keyword extraction tool for model training and testing. By interpreting our model, we identified which features of variants are important. Besides, we achieved a satisfactory result on finding the target variant in our testing data set. After adopting the HPO terms by looking up the databases, the top 10 ranking list can be increased to 93.5% (101/108). The performance of the model is similar to that of manual analysis, and it has been used to help National Taiwan University Hospital with a genetic diagnosis.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».