Dataset Information

Cross-Ontology multi-level association rule mining in the Gene Ontology.

ABSTRACT: The Gene Ontology (GO) has become the internationally accepted standard for representing function, process, and location aspects of gene products. The wealth of GO annotation data provides a valuable source of implicit knowledge of relationships among these aspects. We describe a new method for association rule mining to discover implicit co-occurrence relationships across the GO sub-ontologies at multiple levels of abstraction. Prior work on association rule mining in the GO has concentrated on mining knowledge at a single level of abstraction and/or between terms from the same sub-ontology. We have developed a bottom-up generalization procedure called Cross-Ontology Data Mining-Level by Level (COLL) that takes into account the structure and semantics of the GO, generates generalized transactions from annotation data and mines interesting multi-level cross-ontology association rules. We applied our method on publicly available chicken and mouse GO annotation datasets and mined 5368 and 3959 multi-level cross ontology rules from the two datasets respectively. We show that our approach discovers more and higher quality association rules from the GO as evaluated by biologists in comparison to previously published methods. Biologically interesting rules discovered by our method reveal unknown and surprising knowledge about co-occurring GO terms.

SUBMITTER: Manda P

PROVIDER: S-EPMC3470562 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Cross-Ontology multi-level association rule mining in the Gene Ontology.

Manda Prashanti P Ozkan Seval S Wang Hui H McCarthy Fiona F Bridges Susan M SM

PloS one 20121012 10

The Gene Ontology (GO) has become the internationally accepted standard for representing function, process, and location aspects of gene products. The wealth of GO annotation data provides a valuable source of implicit knowledge of relationships among these aspects. We describe a new method for association rule mining to discover implicit co-occurrence relationships across the GO sub-ontologies at multiple levels of abstraction. Prior work on association rule mining in the GO has concentrated on ...[more]

PMID: 23071802

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Project description:BackgroundStudies have shown that in the genome of human immunodeficiency virus (HIV-1) regions responsible for interactions with the host's immune system, namely, cytotoxic T-lymphocyte (CTL) epitopes tend to cluster together in relatively conserved regions. On the other hand, "epitope-less" regions or regions with relatively low density of epitopes tend to be more variable. However, very little is known about relationships among epitopes from different genes, in other words, whether particular epitopes from different genes would occur together in the same viral genome. To identify CTL epitopes in different genes that co-occur in HIV genomes, association rule mining was used.ResultsUsing a set of 189 best-defined HIV-1 CTL/CD8+ epitopes from 9 different protein-coding genes, as described by Frahm, Linde & Brander (2007), we examined the complete genomic sequences of 62 reference HIV sequences (including 13 subtypes and sub-subtypes with approximately 4 representative sequences for each subtype or sub-subtype, and 18 circulating recombinant forms). The results showed that despite inclusion of recombinant sequences that would be expected to break-up associations of epitopes in different genes when two different genomes are recombined, there exist particular combinations of epitopes (epitope associations) that occur repeatedly across the world-wide population of HIV-1. For example, Pol epitope LFLDGIDKA is found to be significantly associated with epitopes GHQAAMQML and FLKEKGGL from Gag and Nef, respectively, and this association rule is observed even among circulating recombinant forms.ConclusionWe have identified CTL epitope combinations co-occurring in HIV-1 genomes including different subtypes and recombinant forms. Such co-occurrence has important implications for design of complex vaccines (multi-epitope vaccines) and/or drugs that would target multiple HIV-1 regions at once and, thus, may be expected to overcome challenges associated with viral escape.

Project description:BackgroundProteins, individual cells, and cell populations denote different levels of an organizational hierarchy, each of which with its own dynamics. Multi-level modeling is concerned with describing a system at these different levels and relating their dynamics. Rule-based modeling has increasingly attracted attention due to enabling a concise and compact description of biochemical systems. In addition, it allows different methods for model analysis, since more than one semantics can be defined for the same syntax.ResultsMulti-level modeling implies the hierarchical nesting of model entities and explicit support for downward and upward causation between different levels. Concepts to support multi-level modeling in a rule-based language are identified. To those belong rule schemata, hierarchical nesting of species, assigning attributes and solutions to species at each level and preserving content of nested species while applying rules. Further necessities are the ability to apply rules and flexibly define reaction rate kinetics and constraints on nested species as well as species that are nested within others. An example model is presented that analyses the interplay of an intracellular control circuit with states at cell level, its relation to cell division, and connections to intercellular communication within a population of cells. The example is described in ML-Rules - a rule-based multi-level approach that has been realized within the plug-in-based modeling and simulation framework JAMES II.ConclusionsRule-based languages are a suitable starting point for developing a concise and compact language for multi-level modeling of cell biological systems. The combination of nesting species, assigning attributes, and constraining reactions according to these attributes is crucial in achieving the desired expressiveness. Rule schemata allow a concise and compact description of complex models. As a result, the presented approach facilitates developing and maintaining multi-level models that, for instance, interrelate intracellular and intercellular dynamics.

Project description:BackgroundThe COVID-19 pandemic is a significant public health crisis that is hitting hard on people's health, well-being, and freedom of movement, and affecting the global economy. Scientists worldwide are competing to develop therapeutics and vaccines; currently, three drugs and two vaccine candidates have been given emergency authorization use. However, there are still questions of efficacy with regard to specific subgroups of patients and the vaccine's scalability to the general public. Under such circumstances, understanding COVID-19 symptoms is vital in initial triage; it is crucial to distinguish the severity of cases for effective management and treatment. This study aimed to discover symptom patterns and overall symptom rules, including rules disaggregated by age, sex, chronic condition, and mortality status, among COVID-19 patients.MethodsThis study was a retrospective analysis of COVID-19 patient data made available online by the Wolfram Data Repository through May 27, 2020. We applied a widely used rule-based machine learning technique called association rule mining to identify frequent symptoms and define patterns in the rules discovered.ResultIn total, 1,560 patients with COVID-19 were included in the study, with a median age of 52 years. The most frequently occurring symptom was fever (67%), followed by cough (37%), malaise/body soreness (11%), pneumonia (11%), and sore throat (8%). Myocardial infarction, heart failure, and renal disease were present in less than 1% of patients. The top ten significant symptom rules (out of 71 generated) showed cough, septic shock, and respiratory distress syndrome as frequent consequents. If a patient had a breathing problem and sputum production, then, there was higher confidence of that patient having a cough; if cardiac disease, renal disease, or pneumonia was present, then there was a higher confidence of septic shock or respiratory distress syndrome. Symptom rules differed between younger and older patients and between male and female patients. Patients who had chronic conditions or died of COVID-19 had more severe symptom rules than those patients who did not have chronic conditions or survived of COVID-19. Concerning chronic condition rules among 147 patients, if a patient had diabetes, prerenal azotemia, and coronary bypass surgery, there was a certainty of hypertension.ConclusionThe most frequently reported symptoms in patients with COVID-19 were fever, cough, pneumonia, and sore throat; while 1% had severe symptoms, such as septic shock, respiratory distress syndrome, and respiratory failure. Symptom rules differed by age and sex. Patients with chronic disease and patients who died of COVID-19 had severe symptom rules more specifically, cardiovascular-related symptoms accompanied by pneumonia, fever, and cough as consequents.

Dataset Information

Cross-Ontology multi-level association rule mining in the Gene Ontology.

Publications

Cross-Ontology multi-level association rule mining in the Gene Ontology.

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