Dataset Information

An interpretable low-complexity machine learning framework for robust exome-based in-silico diagnosis of Crohn's disease patients.

ABSTRACT: Whole exome sequencing (WES) data are allowing researchers to pinpoint the causes of many Mendelian disorders. In time, sequencing data will be crucial to solve the genome interpretation puzzle, which aims at uncovering the genotype-to-phenotype relationship, but for the moment many conceptual and technical problems need to be addressed. In particular, very few attempts at the in-silico diagnosis of oligo-to-polygenic disorders have been made so far, due to the complexity of the challenge, the relative scarcity of the data and issues such as batch effects and data heterogeneity, which are confounder factors for machine learning (ML) methods. Here, we propose a method for the exome-based in-silico diagnosis of Crohn's disease (CD) patients which addresses many of the current methodological issues. First, we devise a rational ML-friendly feature representation for WES data based on the gene mutational burden concept, which is suitable for small sample sizes datasets. Second, we propose a Neural Network (NN) with parameter tying and heavy regularization, in order to limit its complexity and thus the risk of over-fitting. We trained and tested our NN on 3 CD case-controls datasets, comparing the performance with the participants of previous CAGI challenges. We show that, notwithstanding the limited NN complexity, it outperforms the previous approaches. Moreover, we interpret the NN predictions by analyzing the learned patterns at the variant and gene level and investigating the decision process leading to each prediction.

SUBMITTER: Raimondi D

PROVIDER: S-EPMC7671306 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An interpretable low-complexity machine learning framework for robust exome-based in-silico diagnosis of Crohn's disease patients.

Raimondi Daniele D Simm Jaak J Arany Adam A Fariselli Piero P Cleynen Isabelle I Moreau Yves Y

NAR genomics and bioinformatics 20200221 1

Whole exome sequencing (WES) data are allowing researchers to pinpoint the causes of many Mendelian disorders. In time, sequencing data will be crucial to solve the genome interpretation puzzle, which aims at uncovering the genotype-to-phenotype relationship, but for the moment many conceptual and technical problems need to be addressed. In particular, very few attempts at the in-silico diagnosis of oligo-to-polygenic disorders have been made so far, due to the complexity of the challenge ...[more]

PMID: 33575557

Similar Datasets

Project description:ObjectivePostoperative red blood cell (RBC) transfusion is widely used during the perioperative period but is often associated with a high risk of infection and complications. However, prediction models for RBC transfusion in patients with orthopedic surgery have not yet been developed. We aimed to identify predictors and constructed prediction models for RBC transfusion after orthopedic surgery using interpretable machine learning algorithms.MethodsThis retrospective cohort study reviewed a total of 59,605 patients undergoing orthopedic surgery from June 2013 to January 2019 across 7 tertiary hospitals in China. Patients were randomly split into training (80%) and test subsets (20%). The feature selection method of recursive feature elimination (RFE) was used to identify an optimal feature subset from thirty preoperative variables, and six machine learning algorithms were applied to develop prediction models. The Shapley Additive exPlanations (SHAP) value was employed to evaluate the contribution of each predictor towards the prediction of postoperative RBC transfusion. For simplicity of the clinical utility, a risk score system was further established using the top risk factors identified by machine learning models.ResultsOf the 59,605 patients with orthopedic surgery, 19,921 (33.40%) underwent postoperative RBC transfusion. The CatBoost model exhibited an AUC of 0.831 (95% CI: 0.824-0.836) on the test subset, which significantly outperformed five other prediction models. The risk of RBC transfusion was associated with old age (>60 years) and low RBC count (<4.0 × 1012/L) with clear threshold effects. Extremes of BMI, low albumin, prolonged activated partial thromboplastin time, repair and plastic operations on joint structures were additional top predictors for RBC transfusion. The risk score system derived from six risk factors performed well with an AUC of 0.801 (95% CI: 0.794-0.807) on the test subset.ConclusionBy applying an interpretable machine learning framework in a large-scale multicenter retrospective cohort, we identified novel modifiable risk factors and developed prediction models with good performance for postoperative RBC transfusion in patients undergoing orthopedic surgery. Our findings may allow more precise identification of high-risk patients for optimal control of risk factors and achieve personalized RBC transfusion for orthopedic patients.

Dataset Information

An interpretable low-complexity machine learning framework for robust exome-based in-silico diagnosis of Crohn's disease patients.

Publications

An interpretable low-complexity machine learning framework for robust exome-based <i>in</i>-<i>silico</i> diagnosis of Crohn's disease patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets