Predicting Rules for Cancer Subtype Classification using Grammar-Based Genetic Programming on various Genomic Data Types

With the advent of high-throughput methods more genomic data then ever has been generated during the past decade. As these technologies remain cost intensive and not worthwhile for every research group, databases, such as the TCGA and Firebrowse, emerged. While these database enable the fast and free access to massive amounts of genomic data, they also embody new challenges to the research community. This study investigates methods to obtain, normalize and process genomic data for computer aided decision making in the field of cancer subtype discovery. A new software, termed FirebrowseR is introduced, allowing the direct download of genomic data sets into the R programming environment. To pre-process the obtained data, a set of methods is introduced, enabling data type specific normalization. As a proof of principle, the Web-TCGA software is created, enabling fast data analysis. To explore cancer subtypes a statistical model, the EDL, is introduced. The newly developed method is designed to provide highly precise, yet interpretable models. The EDL is tested on well established data sets, while its performance is compared to state of the art machine learning algorithms. As a proof of principle, the EDL was run on a cohort of 1,000 breast cancer patients, where it reliably re-identified the known subtypes and automatically selected the corresponding maker genes, by which the subtypes are defined. In addition, novel patterns of alterations in well known maker genes could be identified to distinguish primary and mCRPC samples. The findings suggest that mCRPC is characterized through a unique amplification of the Androgen Receptor, while a significant fraction of primary samples is described by a loss of heterozygosity TP53 and NCOR1

University of Dayton Magazine, Spring 2014

This issue includes articles on a high biology teacher, how technology has changed behavior, and the WVUD-FM radio station.https://ecommons.udayton.edu/dayton_mag/1034/thumbnail.jp

Seeking multiple solutions:an updated survey on niching methods and their applications

Multi-Modal Optimization (MMO) aiming to locate multiple optimal (or near-optimal) solutions in a single simulation run has practical relevance to problem solving across many fields. Population-based meta-heuristics have been shown particularly effective in solving MMO problems, if equipped with specificallydesigned diversity-preserving mechanisms, commonly known as niching methods. This paper provides an updated survey on niching methods. The paper first revisits the fundamental concepts about niching and its most representative schemes, then reviews the most recent development of niching methods, including novel and hybrid methods, performance measures, and benchmarks for their assessment. Furthermore, the paper surveys previous attempts at leveraging the capabilities of niching to facilitate various optimization tasks (e.g., multi-objective and dynamic optimization) and machine learning tasks (e.g., clustering, feature selection, and learning ensembles). A list of successful applications of niching methods to real-world problems is presented to demonstrate the capabilities of niching methods in providing solutions that are difficult for other optimization methods to offer. The significant practical value of niching methods is clearly exemplified through these applications. Finally, the paper poses challenges and research questions on niching that are yet to be appropriately addressed. Providing answers to these questions is crucial before we can bring more fruitful benefits of niching to real-world problem solving

Using machine learning to support better and intelligent visualisation for genomic data

Massive amounts of genomic data are created for the advent of Next Generation Sequencing technologies. Great technological advances in methods of characterising the human diseases, including genetic and environmental factors, make it a great opportunity to understand the diseases and to find new diagnoses and treatments. Translating medical data becomes more and more rich and challenging. Visualisation can greatly aid the processing and integration of complex data. Genomic data visual analytics is rapidly evolving alongside with advances in high-throughput technologies such as Artificial Intelligence (AI), and Virtual Reality (VR). Personalised medicine requires new genomic visualisation tools, which can efficiently extract knowledge from the genomic data effectively and speed up expert decisions about the best treatment of an individual patient’s needs. However, meaningful visual analysis of such large genomic data remains a serious challenge. Visualising these complex genomic data requires not only simply plotting of data but should also lead to better decisions. Machine learning has the ability to make prediction and aid in decision-making. Machine learning and visualisation are both effective ways to deal with big data, but they focus on different purposes. Machine learning applies statistical learning techniques to automatically identify patterns in data to make highly accurate prediction, while visualisation can leverage the human perceptual system to interpret and uncover hidden patterns in big data. Clinicians, experts and researchers intend to use both visualisation and machine learning to analyse their complex genomic data, but it is a serious challenge for them to understand and trust machine learning models in the serious medical industry. The main goal of this thesis is to study the feasibility of intelligent and interactive visualisation which combined with machine learning algorithms for medical data analysis. A prototype has also been developed to illustrate the concept that visualising genomics data from childhood cancers in meaningful and dynamic ways could lead to better decisions. Machine learning algorithms are used and illustrated during visualising the cancer genomic data in order to provide highly accurate predictions. This research could open a new and exciting path to discovery for disease diagnostics and therapies

Cancer-inspired Genomics Mapper Model for the Generation of Synthetic DNA Sequences with Desired Genomics Signatures

Genome data are crucial in modern medicine, offering significant potential for diagnosis and treatment. Thanks to technological advancements, many millions of healthy and diseased genomes have already been sequenced; however, obtaining the most suitable data for a specific study, and specifically for validation studies, remains challenging with respect to scale and access. Therefore, in silico genomics sequence generators have been proposed as a possible solution. However, the current generators produce inferior data using mostly shallow (stochastic) connections, detected with limited computational complexity in the training data. This means they do not take the appropriate biological relations and constraints, that originally caused the observed connections, into consideration. To address this issue, we propose cancer-inspired genomics mapper model (CGMM), that combines genetic algorithm (GA) and deep learning (DL) methods to tackle this challenge. CGMM mimics processes that generate genetic variations and mutations to transform readily available control genomes into genomes with the desired phenotypes. We demonstrate that CGMM can generate synthetic genomes of selected phenotypes such as ancestry and cancer that are indistinguishable from real genomes of such phenotypes, based on unsupervised clustering. Our results show that CGMM outperforms four current state-of-the-art genomics generators on two different tasks, suggesting that CGMM will be suitable for a wide range of purposes in genomic medicine, especially for much-needed validation studies

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rs2735383, located at a microRNA binding site in the 3 ' UTR of NBS1, is not associated with breast cancer risk

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r(2) > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.Peer reviewe