José Palma

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.

Raquel Espinosa, Fernando Jiménez, José Palma

Time series forecasting plays a crucial role in diverse fields, necessitating the development of robust models that can effectively handle complex temporal patterns. In this article, we present a novel feature selection method embedded in Long Short-Term Memory networks, leveraging a multi-objective evolutionary algorithm. Our approach optimizes the weights and biases of the LSTM in a partitioned manner, with each objective function of the evolutionary algorithm targeting the root mean square error in a specific data partition. The set of non-dominated forecast models identified by the algorithm is then utilized to construct a meta-model through stacking-based ensemble learning. Furthermore, our proposed method provides an avenue for attribute importance determination, as the frequency of selection for each attribute in the set of non-dominated forecasting models reflects their significance. This attribute importance insight adds an interpretable dimension to the forecasting process. Experimental evaluations on air quality time series data from Italy and southeast Spain demonstrate that our method substantially improves the generalization ability of conventional LSTMs, effectively reducing overfitting. Comparative analyses against state-of-the-art CancelOut and EAR-FS methods highlight the superior performance of our approach.

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.