Biology subjects

Karwath, A.

Publications and source records attributed to Karwath, A..

5 recordsLinked to original sources

bioRxiv2021

Klarigi: Explanations for Semantic Groupings

BackgroundAnnotation of biomedical entities with ontology classes provides for formal semantic analysis and mobilisation of background knowledge in determining their relationships. To date enrichment analysis has been routinely employed to identify classes that are over-represented in annotations across sets of groups, such as biosample gene expression profiles or patient phenotypes. These approaches, however, usually consider only univariate relationships, make limited use of the semantic features of ontologies, and provide limited information and evaluation of the explanatory power of both singular and grouped candidate classes. Moreover, they do not solve the problem of deriving cohesive, characteristic, and discriminatory sets of classes for entity groups. ResultsWe have developed a new method, Klarigi, which introduces multiple scoring heuristics for identification of classes that are both compositional and discriminatory for groups of entities annotated with ontology classes. The tool includes a novel algorithm for derivation of multivariable semantic explanations for entity groups, makes use of semantic inference through live use of an ontology reasoner, and includes a classification method for identifying the discriminatory power of candidate sets. We describe the design and implementation of Klarigi, and evaluate its use in two test cases, comparing and contrasting methods and results with literature and enrichment analysis methods. ConclusionsWe demonstrate that Klarigi produces characteristic and discriminatory explanations for groups of biomedical entities in two settings. We also show that these explanations recapitulate and extend the knowledge held in existing biomedical databases and literature for several diseases. We conclude that Klarigi provides a distinct and valuable perspective on biomedical datasets when compared with traditional enrichment methods, and therefore constitutes a new method by which biomedical datasets can be explored, contributing to improved insight into semantic data.

bioinformatics↗

bioRxiv2021

Towards Similarity-based Differential Diagnostics For Common Diseases

Ontology-based phenotype profiles have been utilised for the purpose of differential diagnosis of rare genetic diseases, and for decision support in specific disease domains. Particularly, semantic similarity facilitates diagnostic hypothesis generation through comparison with disease phenotype profiles. However, the approach has not been applied for differential diagnosis of common diseases, or generalised clinical diagnostics from uncurated text-derived phenotypes. In this work, we describe the development of an approach for deriving patient phenotype profiles from clinical narrative text, and apply this to text associated with MIMIC-III patient visits. We then explore the use of semantic similarity with those text-derived phenotypes to classify primary patient diagnosis, comparing the use of patient-patient similarity and patient-disease similarity using phenotype-disease profiles previously mined from literature. We also consider a combined approach, in which literature-derived phenotypes are extended with the content of text-derived phenotypes we mined from 500 patients. The results reveal a powerful approach, showing that in one setting, uncurated text phenotypes can be used for differential diagnosis of common diseases, making use of information both inside and outside the setting. While the methods themselves should be explored for further optimisation, they could be be applied to a variety of clinical tasks, such as differential diagnosis, cohort discovery, document and text classification, and outcome prediction.

bioinformatics↗

bioRxiv2020

Exploring binary relations for ontology extension and improved adaptation to clinical text

BackgroundThe controlled domain vocabularies provided by ontologies make them an indispensable tool for text mining. Ontologies also include semantic features in the form of taxonomy and axioms, which make annotated entities in text corpora useful for semantic analysis. Extending those semantic features may improve performance for characterisation and analytic tasks. Ontology learning techniques have previously been explored for novel ontology construction from text, though most recent approaches have focused on literature, with applications in information retrieval or human interaction tasks. We hypothesise that extension of existing ontologies using information mined from clinical narrative text may help to adapt those ontologies such that they better characterise those texts, and lead to improved classification performance. ResultsWe develop and present a framework for identifying new classes in text corpora, which can be integrated into existing ontology hierarchies. To do this, we employ the Stanford Open Information Extraction algorithm and integrate its implementation into the Komenti semantic text mining framework. To identify whether our approach leads to better characterisation of text, we present a case study, using the method to learn an adaptation to the Disease Ontology using text associated with a sample of 1,000 patient visits from the MIMIC-III critical care database. We use the adapted ontology to annotate and classify shared first diagnosis on patient visits with semantic similarity, revealing an improved performance over use of the base Disease Ontology on the set of visits the ontology was constructed from. Moreover, we show that the adapted ontology also improved performance for the same task over two additional unseen samples of 1,000 and 2,500 patient visits. ConclusionsWe report a promising new method for ontology learning and extension from text. We demonstrate that we can successfully use the method to adapt an existing ontology to a textual dataset, improving its ability to characterise the dataset, and leading to improved analytic performance, even on unseen portions of the dataset.

bioinformatics↗

bioRxiv2019

Ontology-based prediction of cancer driver genes

Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity, many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.

bioinformatics↗

bioRxiv2018

Vec2SPARQL: integrating SPARQL queries and knowledge graph embeddings

Recent developments in machine learning have lead to a rise of large number of methods for extracting features from structured data. The features are represented as a vectors and may encode for some semantic aspects of data. They can be used in a machine learning models for different tasks or to compute similarities between the entities of the data. SPARQL is a query language for structured data originally developed for querying Resource Description Framework (RDF) data. It has been in use for over a decade as a standardized NoSQL query language. Many different tools have been developed to enable data sharing with SPARQL. For example, SPARQL endpoints make your data interoperable and available to the world. SPARQL queries can be executed across multiple endpoints. We have developed a Vec2SPARQL, which is a general framework for integrating structured data and their vector space representations. Vec2SPARQL allows jointly querying vector functions such as computing similarities (cosine, correlations) or classifications with machine learning models within a single SPARQL query. We demonstrate applications of our approach for biomedical and clinical use cases. Our source code is freely available at https://github.com/bio-ontology-research-group/vec2sparql and we make a Vec2SPARQL endpoint available at http://sparql.bio2vec.net/.

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