Computational Hybrid Systems for Identifying Prognostic Gene Markers of Lung Cancer

Lung cancer is the most fatal cancer around the world. Current lung cancer prognosis and treatment is based on tumor stage population statistics and could not reliably assess the risk for developing recurrence in individual patients. Biomarkers enable treatment options to be tailored to individual patients based on their tumor molecular characteristics. To date, there is no clinically applied molecular prognostic model for lung cancer. Statistics and feature selection methods identify gene candidates by ranking the association between gene expression and disease outcome, but do not account for the interactions among genes. Computational network methods could model interactions, but have not been used for gene selection due to computational inefficiency. Moreover, the curse of dimensionality in human genome data imposes more computational challenges to these methods.;We proposed two hybrid systems for the identification of prognostic gene signatures for lung cancer using gene expressions measured with DNA microarray. The first hybrid system combined t-tests, Statistical Analysis of Microarray (SAM), and Relief feature selections in multiple gene filtering layers. This combinatorial system identified a 12-gene signature with better prognostic performance than published signatures in treatment selection for stage I and II patients (log-rank P\u3c0.04, Kaplan-Meier analyses). The 12-gene signature is a more significant prognostic factor (hazard ratio=4.19, 95% CI: [2.08, 8.46], P\u3c0.00006) than other clinical covariates. The signature genes were found to be involved in tumorigenesis in functional pathway analyses.;The second proposed system employed a novel computational network model, i.e., implication networks based on prediction logic. This network-based system utilizes gene coexpression networks and concurrent coregulation with signaling pathways for biomarker identification. The first application of the system modeled disease-mediated genome-wide coexpression networks. The entire genomic space were extensively explored and 21 gene signatures were discovered with better prognostic performance than all published signatures in stage I patients not receiving chemotherapy (hazard ratio\u3e1, CPE\u3e0.5, P \u3c 0.05). These signatures could potentially be used for selecting patients for adjuvant chemotherapy. The second application of the system modeled the smoking-mediated coexpression networks and identified a smoking-associated 7-gene signature. The 7-gene signature generated significant prognostication specific to smoking lung cancer patients (log-rank P\u3c0.05, Kaplan-Meier analyses), with implications in diagnostic screening of lung cancer risk in smokers (overall accuracy=74%, P\u3c0.006). The coexpression patterns derived from the implication networks in both applications were successfully validated with molecular interactions reported in the literature (FDR\u3c0.1).;Our studies demonstrated that hybrid systems with multiple gene selection layers outperform traditional methods. Moreover, implication networks could efficiently model genome-scale disease-mediated coexpression networks and crosstalk with signaling pathways, leading to the identification of clinically important gene signatures

Deep learning cardiac motion analysis for human survival prediction

Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimising the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimised for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients the predictive accuracy (quantified by Harrell's C-index) was significantly higher (p < .0001) for our model C=0.73 (95$\%$ CI: 0.68 - 0.78) than the human benchmark of C=0.59 (95$\%$ CI: 0.53 - 0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival

A survey on computational intelligence approaches for predictive modeling in prostate cancer

Predictive modeling in medicine involves the development of computational models which are capable of analysing large amounts of data in order to predict healthcare outcomes for individual patients. Computational intelligence approaches are suitable when the data to be modelled are too complex forconventional statistical techniques to process quickly and eciently. These advanced approaches are based on mathematical models that have been especially developed for dealing with the uncertainty and imprecision which is typically found in clinical and biological datasets. This paper provides a survey of recent work on computational intelligence approaches that have been applied to prostate cancer predictive modeling, and considers the challenges which need to be addressed. In particular, the paper considers a broad definition of computational intelligence which includes evolutionary algorithms (also known asmetaheuristic optimisation, nature inspired optimisation algorithms), Artificial Neural Networks, Deep Learning, Fuzzy based approaches, and hybrids of these,as well as Bayesian based approaches, and Markov models. Metaheuristic optimisation approaches, such as the Ant Colony Optimisation, Particle Swarm Optimisation, and Artificial Immune Network have been utilised for optimising the performance of prostate cancer predictive models, and the suitability of these approaches are discussed

A Review of Atrial Fibrillation Detection Methods as a Service

Atrial Fibrillation (AF) is a common heart arrhythmia that often goes undetected, and even if it is detected, managing the condition may be challenging. In this paper, we review how the RR interval and Electrocardiogram (ECG) signals, incorporated into a monitoring system, can be useful to track AF events. Were such an automated system to be implemented, it could be used to help manage AF and thereby reduce patient morbidity and mortality. The main impetus behind the idea of developing a service is that a greater data volume analyzed can lead to better patient outcomes. Based on the literature review, which we present herein, we introduce the methods that can be used to detect AF efficiently and automatically via the RR interval and ECG signals. A cardiovascular disease monitoring service that incorporates one or multiple of these detection methods could extend event observation to all times, and could therefore become useful to establish any AF occurrence. The development of an automated and efficient method that monitors AF in real time would likely become a key component for meeting public health goals regarding the reduction of fatalities caused by the disease. Yet, at present, significant technological and regulatory obstacles remain, which prevent the development of any proposed system. Establishment of the scientific foundation for monitoring is important to provide effective service to patients and healthcare professionals