Regulatory network discovery using heuristics

This thesis improves the GRN discovery process by integrating heuristic information via a co-regulation function, a post-processing procedure, and a Hub Network algorithm to build the backbone of the network.Doctor of Philosoph

Inference of gene expression networks using memetic gene expression programming

In this paper we aim to infer a model of genetic networks from time series data of gene expression profiles by using a new gene expression programming algorithm. Gene expression networks are modelled by differential equations which represent temporal gene expression relations. Gene Expression Programming is a new extension of genetic programming. Here we combine a local search method with gene expression programming to form a memetic algorithm in order to find not only the system of differential equations but also fine tune its constant parameters. The effectiveness of the proposed method is justified by comparing its performance with that of conventional genetic programming applied to this problem in previous studies

Integrating biological heuristics and gene expression data for gene regulatory network inference

Gene Regulatory Networks (GRNs) offer enhanced insight into the biological functions and biochemical pathways of cells associated with gene regulatory mechanisms. However, obtaining accurate GRNs that explain gene expressions and functional associations remains a difficult task. Only a few studies have incorporated heuristics into a GRN discovery process. Doing so has the potential to improve accuracy and reduce the search space and computational time. A technique for GRN discovery that integrates heuristic information into the discovery process is advanced. The approach incorporates three elements: 1) a novel 2D visualized coexpression function that measures the association between genes; 2) a post-processing step that improves detection of up, down and self-regulation and 3) the application of heuristics to generate a Hub network as the backbone of the GRN. Using available microarray and next generation sequencing data from Escherichia coli, six synthetic benchmark GRN datasets were generated with the neighborhood addition and cluster addition methods available in SynTReN. Results of the novel 2D-visualization co-expression function were compared with results obtained using Pearson's correlation and mutual information. The performance of the biological genetics-based heuristics consisting of the 2D-Visualized Co-expression function, post-processing and Hub network was then evaluated by comparing the performance to the GRNs obtained by ARACNe and CLR. The 2D-Visualized Co-expression function significantly improved gene-gene association matching compared to Pearson's correlation coefficient (t = 3.46, df = 5, p = 0.02) and Mutual Information (t = 4.42, df = 5, p = 0.007). The heuristics model gave a 60% improvement against ARACNe (p = 0.02) and CLR (p = 0.019). Analysis of Escherichia coli data suggests that the GRN discovery technique proposed is capable of identifying significant transcriptional regulatory interactions and the corresponding regulatory networks

A heuristic gene regulatory networks model for cardiac function and pathology

Genome-wide association studies (GWAS) and next-generation sequencing (NGS) has led to an increase in information about the human genome and cardiovascular disease. Understanding the role of genes in cardiac function and pathology requires modeling gene interactions and identification of regulatory genes as part of a gene regulatory network (GRN). Feature selection and data reduction not sufficient and require domain knowledge to deal with large data. We propose three novel innovations in constructing a GRN based on heuristics. A 2D Visualised Co-regulation function. Post-processing to identify gene-gene interactions. Finally a threshold algorithm is applied to identify the hub genes that provide the backbone of the GRN. The 2D Visualized Co-regulation function performed significantly better compared to the Pearson's correlation for measuring pairwise associations (t=3.46, df=5, p=0.018). The F-measure, improved from 0.11 to 0.12. The hub network provided a 60% improvement to that reported in the literature. The performance of the hub network was then also compared against ARACNe and performed significantly better (p=0.024). We conclude that a heuristics approach in developing GRNs has potential to improve our understanding of gene regulation and interaction in diverse biological function and disease

Emerging point of care devices and artificial intelligence : prospects and challenges for public health

Risk assessments for numerous conditions can now be performed cost-effectively and accurately using emerging point of care devices coupled with machine learning algorithms. In this article, the case is advanced that point of care testing in combination with risk assessments generated with artificial intelligence algorithms, applied to the universal screening of the general public for multiple conditions at one session, represents a new kind of in-expensive screening that can lead to the early detection of disease and other public health benefits. A case study of a diabetes screening clinic in a rural area of Australia is presented to illustrate its benefits. Universal, poly-aetiological screening is shown to meet the ten World Health Organisation criteria for screening programmes. © Elsevier Inc