Juan A. Botía

José A. Pardo, Tomás Bernal, Jaime Ñiguez et al.

Inconsistencies between clinical and omics data may arise within medical cohorts. The identification, annotation and explanation of anomalous omics-based patients or individuals may become crucial to better reshape the disease, e.g., by detecting early onsets signaled by the omics and undetectable from observable symptoms. Here, we developed MLASDO (Machine Learning based Anomalous Sample Detection on Omics), a new method and software tool to identify, characterize and automatically describe anomalous samples based on omics data. Its workflow is based on three steps: (1) classification of healthy and cases individuals using a support vector machine algorithm; (2) detection of anomalous samples within groups; (3) explanation of anomalous individuals based on clinical data and expert knowledge. We showcase MLASDO using transcriptomics data of 317 healthy controls (HC) and 465 Parkinson's disease (PD) cases from the Parkinson's Progression Markers Initiative. In this cohort, MLASDO detected 15 anomalous HC with a PD-like transcriptomic signature and PD-like clinical features, including a lower proportion of CD4/CD8 naive T-cells and CD4 memory T-cells compared to HC (P<3.5*10^-3). MLASDO also identified 22 anomalous PD cases with a transcriptomic signature more similar to that of HC and some clinical features more similar to HC, including a lower proportion of mature neutrophils compared to PD cases (P<6*10^-3). In summary, MLASDO is a powerful tool that can help the clinician to detect and explain anomalous HC and cases of interest to be followed up. MLASDO is an open-source R package available at: https://github.com/JoseAdrian3/MLASDO.

José A. Pardo, Alicia Gómez-Pascual, José T. Palma et al.

The growing volume of omics and clinical data generated for neurodegenerative diseases (NDs) requires new approaches for their curation so they can be ready-to-use in bioinformatics. NeuroEmbed is an approach for the engineering of semantically accurate embedding spaces to represent cohorts and samples. The NeuroEmbed method comprises four stages: (1) extraction of ND cohorts from public repositories; (2) semi-automated normalization and augmentation of metadata of cohorts and samples using biomedical ontologies and clustering on the embedding space; (3) automated generation of a natural language question-answering (QA) dataset for cohorts and samples based on randomized combinations of standardized metadata dimensions and (4) fine-tuning of a domain-specific embedder to optimize queries. We illustrate the approach using the GEO repository and the PubMedBERT pretrained embedder. Applying NeuroEmbed, we semantically indexed 2,801 repositories and 150,924 samples. Amongst many biology-relevant categories, we normalized more than 1,700 heterogeneous tissue labels from GEO into 326 unique ontology-aligned concepts and enriched annotations with new ontology-aligned terms, leading to a fold increase in size for the metadata terms between 2.7 and 20 fold. After fine-tuning PubMedBERT with the QA training data augmented with the enlarged metadata, the model increased its mean Retrieval Precision from 0.277 to 0.866 and its mean Percentile Rank from 0.355 to 0.896. The NeuroEmbed methodology for the creation of electronic catalogues of omics cohorts and samples will foster automated bioinformatic pipelines construction. The NeuroEmbed catalogue of cohorts and samples is available at https://github.com/JoseAdrian3/NeuroEmbed.

Antonio Guillén-Teruel, Marcos Caracena, Jose A. Pardo et al.

This research addresses the challenges of handling unbalanced datasets for binary classification tasks. In such scenarios, standard evaluation metrics are often biased by the disproportionate representation of the minority class. Conducting experiments across seven datasets, we uncovered inconsistencies in evaluation metrics when determining the model that outperforms others for each binary classification problem. This justifies the need for a metric that provides a more consistent and unbiased evaluation across unbalanced datasets, thereby supporting robust model selection. To mitigate this problem, we propose a novel metric, the Unbiased Integration Coefficients (UIC), which exhibits significantly reduced bias ($p < 10^{-4}$) towards the minority class compared to conventional metrics. The UIC is constructed by aggregating existing metrics while penalising those more prone to imbalance. In addition, we introduce the Identical Partitions for Imbalance Problems (IPIP) algorithm for imbalanced ML problems, an ensemble-based approach. Our experimental results show that IPIP outperforms other baseline imbalance-aware approaches using Random Forest and Logistic Regression models in three out of seven datasets as assessed by the UIC metric, demonstrating its effectiveness in addressing imbalanced data challenges in binary classification tasks. This new framework for dealing with imbalanced datasets is materialized in the FILM (Framework for Imbalanced Learning Machines) R Package, accessible at https://github.com/antoniogt/FILM.

Jose L. Mellina Andreu, Luis Bernal, Antonio F. Skarmeta et al.

The association of a given human phenotype to a genetic variant remains a critical challenge for biology. We present a novel system called PhenoLinker capable of associating a score to a phenotype-gene relationship by using heterogeneous information networks and a convolutional neural network-based model for graphs, which can provide an explanation for the predictions. This system can aid in the discovery of new associations and in the understanding of the consequences of human genetic variation.

Fernando Jiménez, Gracia Sánchez, José Palma et al.

Gene expression datasets are usually of high dimensionality and therefore require efficient and effective methods for identifying the relative importance of their attributes. Due to the huge size of the search space of the possible solutions, the attribute subset evaluation feature selection methods tend to be not applicable, so in these scenarios feature ranking methods are used. Most of the feature ranking methods described in the literature are univariate methods, so they do not detect interactions between factors. In this paper we propose two new multivariate feature ranking methods based on pairwise correlation and pairwise consistency, which we have applied in three gene expression classification problems. We statistically prove that the proposed methods outperform the state of the art feature ranking methods Clustering Variation, Chi Squared, Correlation, Information Gain, ReliefF and Significance, as well as feature selection methods of attribute subset evaluation based on correlation and consistency with multi-objective evolutionary search strategy.

Mary B. Makarious, Hampton L. Leonard, Dan Vitale et al.

GenoML is a Python package automating machine learning workflows for genomics (genetics and multi-omics) with an open science philosophy. Genomics data require significant domain expertise to clean, pre-process, harmonize and perform quality control of the data. Furthermore, tuning, validation, and interpretation involve taking into account the biology and possibly the limitations of the underlying data collection, protocols, and technology. GenoML's mission is to bring machine learning for genomics and clinical data to non-experts by developing an easy-to-use tool that automates the full development, evaluation, and deployment process. Emphasis is put on open science to make workflows easily accessible, replicable, and transferable within the scientific community. Source code and documentation is available at https://genoml.com.