Machine Learning to Support the Presentation of Complex Pathway Graphs.

in IEEE/ACM transactions on computational biology and bioinformatics (2019)

Visualization of biological mechanisms by means of pathway graphs is necessary to better understand the often complex underlying system. Manual layout of such pathways or maps of knowledge is a difficult ... [more ▼]

Visualization of biological mechanisms by means of pathway graphs is necessary to better understand the often complex underlying system. Manual layout of such pathways or maps of knowledge is a difficult and time consuming process. Node duplication is a technique that makes layouts with improved readability possible by reducing edge crossings and shortening edge lengths in drawn diagrams. In this article we propose an approach using Machine Learning (ML) to facilitate parts of this task by training a Support Vector Machine (SVM) with actions taken during manual biocuration. Our training input is a series of incremental snapshots of a diagram describing mechanisms of a disease, progressively curated by a human expert employing node duplication in the process. As a test of the trained SVM models, they are applied to a single large instance and 25 medium-sized instances of hand-curated biological pathways. Finally, in a user validation study, we compare the model predictions to the outcome of a node duplication questionnaire answered by users of biological pathways with varying experience. We successfully predicted nodes for duplication and emulated human choices, demonstrating that our approach can effectively learn human-like node duplication preferences to support curation of pathway diagrams in various contexts. [less ▲]

Tackling the IFP Problem with the Preference-Based Genetic Algorithm

in Proceedings of the Genetic and Evolutionary Computation Conference 2016 (2016)

A Novel Multi-objectivisation Approach for Optimising the Protein Inverse Folding Problem

in Applications of Evolutionary Computation: 18th European Conference, EvoApplications 2015, Copenhagen, Denmark, April 8-10, 2015, Proceedings (2015)

In biology, the subject of protein structure prediction is of continued interest, not only to chart the molecular map of the living cell, but also to design proteins of new functions. The Inverse Folding ... [more ▼]

In biology, the subject of protein structure prediction is of continued interest, not only to chart the molecular map of the living cell, but also to design proteins of new functions. The Inverse Folding Problem (IFP) is in itself an important research problem, but also at the heart of most rational protein design approaches. In brief, the IFP consists in finding sequences that will fold into a given structure, rather than determining the structure for a given sequence - as in conventional structure prediction. In this work we present a Multi Objective Genetic Algorithm (MOGA) using the diversity-as-objective (DAO) variant of multi-objectivisation, to optimise secondary structure similarity and sequence diversity at the same time, hence pushing the search farther into wide-spread areas of the sequence solution-space. To control the high diversity generated by the DAO approach, we add a novel Quantile Constraint (QC) mechanism to discard an adjustable worst quantile of the population. This DAO-QC approach can efficiently emphasise exploitation rather than exploration to a selectable degree achieving a trade-off producing both better and more diverse sequences than the standard Genetic Algorithm (GA). To validate the final results, a subset of the best sequences was selected for tertiary structure prediction. The super-positioning with the original protein structure demonstrated that meaningful sequences are generated underlining the potential of this work. [less ▲]

NK Landscape Instances Mimicking the Protein Inverse Folding Problem Towards Future Benchmarks

in GECCO Companion '15 Proceedings of the Companion Publication of the 2015 Annual Conference on Genetic and Evolutionary Computation (2015)

This paper introduces two new nominal NK Landscape model instances designed to mimic the properties of one challenging optimisation problem from biology: the Inverse Folding Problem (IFP), here focusing ... [more ▼]

This paper introduces two new nominal NK Landscape model instances designed to mimic the properties of one challenging optimisation problem from biology: the Inverse Folding Problem (IFP), here focusing on a simpler secondary structure version. Through landscape analysis tests, numerous problem properties are identified and used to parameterise and validate model instances in terms of epistatic links, adaptive- and random walk characteristics. Then the performance of different Genetic Algorithms (GAs) is compared on both the new NK Models and the original IFP, in terms of population diversity, solution quality and convergence characteristics. It is demonstrated that very similar properties are captured in all presented tests with a significantly faster evaluation time compared to the real IFP. The future purpose of such a model is to provide a generic benchmark for algorithms targeting protein sequence optimisation, specifically in protein design. It may also provide the foundation for more in-depth studies of the size, shape and characteristics of the solution space of good solutions to the IFP. [less ▲]

Evolutionary multi objective optimisation with diversity as objective for the protein structure similarity problem

Scientific Conference (2014)

Vehicular mobility model optimization using cooperative coevolutionary genetic algorithms

in Proceedings of the Genetic and Evolutionary Computation Conference (GECCO '13) (2013)