Comparing methods for drug-gene interaction prediction on the biomedical literature knowledge graph: performance versus explainability.

This paper applies different link prediction methods on a knowledge graph generated from biomedical literature, with the aim to compare their ability to identify unknown drug-gene interactions and explain their predictions. Identifying novel drug-target interactions is a crucial step in drug discovery and repurposing. One approach to this problem is to predict missing links between drug and gene nodes, in a graph that contains relevant biomedical knowledge. Such a knowledge graph can be extracted from biomedical literature, using text mining tools. In this work, we compare state-of-the-art graph embedding approaches and contextual path analysis on the interaction prediction task. The comparison reveals a trade-off between predictive accuracy and explainability of predictions. Focusing on explainability, we train a decision tree on model predictions and show how it can aid the understanding of the prediction process. We further test the methods on a drug repurposing task and validate the predicted interactions against external databases, with very encouraging results.

Knowledge4COVID-19: A semantic-based approach for constructing a COVID-19 related knowledge graph from various sources and analyzing treatments' toxicities.

In this paper, we present Knowledge4COVID-19, a framework that aims to showcase the power of integrating disparate sources of knowledge to discover adverse drug effects caused by drug-drug interactions among COVID-19 treatments and pre-existing condition drugs. Initially, we focus on constructing the Knowledge4COVID-19 knowledge graph (KG) from the declarative definition of mapping rules using the RDF Mapping Language. Since valuable information about drug treatments, drug-drug interactions, and side effects is present in textual descriptions in scientific databases (e.g., DrugBank) or in scientific literature (e.g., the CORD-19, the Covid-19 Open Research Dataset), the Knowledge4COVID-19 framework implements Natural Language Processing. The Knowledge4COVID-19 framework extracts relevant entities and predicates that enable the fine-grained description of COVID-19 treatments and the potential adverse events that may occur when these treatments are combined with treatments of common comorbidities, e.g., hypertension, diabetes, or asthma. Moreover, on top of the KG, several techniques for the discovery and prediction of interactions and potential adverse effects of drugs have been developed with the aim of suggesting more accurate treatments for treating the virus. We provide services to traverse the KG and visualize the effects that a group of drugs may have on a treatment outcome. Knowledge4COVID-19 was part of the Pan-European hackathon#EUvsVirus in April 2020 and is publicly available as a resource through a GitHub repository and a DOI.

Identifying the presence and severity of dementia by applying interpretable machine learning techniques on structured clinical records.

BACKGROUND: Dementia develops as cognitive abilities deteriorate, and early detection is critical for effective preventive interventions. However, mainstream diagnostic tests and screening tools, such as CAMCOG and MMSE, often fail to detect dementia accurately. Various graph-based or feature-dependent prediction and progression models have been proposed. Whenever these models exploit information in the patients' Electronic Medical Records, they represent promising options to identify the presence and severity of dementia more precisely. METHODS: The methods presented in this paper aim to address two problems related to dementia: (a) Basic diagnosis: identifying the presence of dementia in individuals, and (b) Severity diagnosis: predicting the presence of dementia, as well as the severity of the disease. We formulate these two tasks as classification problems and address them using machine learning models based on random forests and decision tree, analysing structured clinical data from an elderly population cohort. We perform a hybrid data curation strategy in which a dementia expert is involved to verify that curation decisions are meaningful. We then employ the machine learning algorithms that classify individual episodes into a specific dementia class. Decision trees are also used for enhancing the explainability of decisions made by prediction models, allowing medical experts to identify the most crucial patient features and their threshold values for the classification of dementia. RESULTS: Our experiment results prove that baseline arithmetic or cognitive tests, along with demographic features, can predict dementia and its severity with high accuracy. In specific, our prediction models have reached an average f1-score of 0.93 and 0.81 for problems (a) and (b), respectively. Moreover, the decision trees produced for the two issues empower the interpretability of the prediction models. CONCLUSIONS: This study proves that there can be an accurate estimation of the existence and severity of dementia disease by analysing various electronic medical record features and cognitive tests from the episodes of the elderly population. Moreover, a set of decision rules may comprise the building blocks for an efficient patient classification. Relevant clinical and screening test features (e.g. simple arithmetic or animal fluency tasks) represent precise predictors without calculating the scores of mainstream cognitive tests such as MMSE and CAMCOG. Such predictive model can identify not only meaningful features, but also justifications of classification. As a result, the predictive power of machine learning models over curated clinical data is proved, paving the path for a more accurate diagnosis of dementia.

Machine learning methods applied to genotyping data capture interactions between single nucleotide variants in late onset Alzheimer's disease.

Introduction: Genome-wide association studies (GWAS) in late onset Alzheimer's disease (LOAD) provide lists of individual genetic determinants. However, GWAS do not capture the synergistic effects among multiple genetic variants and lack good specificity. Methods: We applied tree-based machine learning algorithms (MLs) to discriminate LOAD (>700 individuals) and age-matched unaffected subjects in UK Biobank with single nucleotide variants (SNVs) from Alzheimer's disease (AD) studies, obtaining specific genomic profiles with the prioritized SNVs. Results: MLs prioritized a set of SNVs located in genes PVRL2, TOMM40, APOE, and APOC1, also influencing gene expression and splicing. The genomic profiles in this region showed interaction patterns involving rs405509 and rs1160985, also present in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. rs405509 located in APOE promoter interacts with rs429358 among others, seemingly neutralizing their predisposing effect. Discussion: Our approach efficiently discriminates LOAD from controls, capturing genomic profiles defined by interactions among SNVs in a hot-spot region.