A novel framework to elucidate core classes in a dataset

In this paper we present an original framework to extract representative groups from a dataset, and we validate it over a novel case study. The framework specifies the application of different clustering algorithms, then several statistical and visualisation techniques are used to characterise the results, and core classes are defined by consensus clustering. Classes may be verified using supervised classification algorithms to obtain a set of rules which may be useful for new data points in the future. This framework is validated over a novel set of histone markers for breast cancer patients. From a technical perspective, the resultant classes are well separated and characterised by low, medium and high levels of biological markers. Clinically, the groups appear to distinguish patients with poor overall survival from those with low grading score and better survival. Overall, this framework offers a promising methodology for elucidating core consensus groups from data

Novel methods to elucidate core classes in multi-dimensional biomedical data

Breast cancer, which is the most common cancer in women, is a complex disease characterised by multiple molecular alterations. Current routine clinical management relies on availability of robust clinical and pathologic prognostic and predictive factors, like the Nottingham Prognostic Index, to support decision making. Recent advances in highthroughput molecular technologies supported the evidence of a biologic heterogeneity of breast cancer. This thesis is a multi-disciplinary work involving both computer scientists and molecular pathologists. It focuses on the development of advanced computational models for the classification of breast cancer into sub-types of the disease based on protein expression levels of selected markers. In a previous study conducted at the University of Nottingham, it has been suggested that immunohistochemical analysis may be used to identify distinct biological classes of breast cancer. The objectives of this work were related both to the clinical and technical aspects. From a clinical point of view, the aim was to encourage a multiple techniques approach when dealing with classification and clustering. From a technical point of view, one of the goals was to verify the stability of groups obtained from different unsupervised clustering algorithms, applied to the same data, and to compare and combine the different solutions with the ones available from the previous study. These aims and objectives were considered in the attempt to fill a number of gaps in the body of knowledge. Several research questions were raised, including how to combine the results obtained by a multi-techniques approach for clustering and whether the medical decision making process could be moved in the direction of personalised healthcare. An original framework to identify core representative classes in a dataset was developed and is described in this thesis. Using different clustering algorithms and several validity indices to explore the best number of groups to split the data, a set of classes may be defined by considering those points that remain stable across different clustering techniques. This set of representative classes may be then characterised resorting to usual statistical techniques and validated using supervised learning. Each step of this framework has been studied separately, resulting in different chapters of this thesis. The whole approach has been successfully applied to a novel set of histone markers for breast cancer provided by the School of Pharmacy at the University of Nottingham. Although further tests are needed to validate and improve the proposed framework, these results make it a good candidate for being transferred to the real world of medical decision making. Other contributions to knowledge may be extracted from this work. Firstly, six breast cancer subtypes have been identified, using consensus clustering, and characterised in terms of clinical outcome. Two of these classes were new in the literature. The second contribution is related to supervised learning. A novel method, based on the naive Bayes classifier, was developed to cope with the non-normality of covariates in many real world problems. This algorithm was validated over known data sets and compared with traditional approaches, obtaining better results in two examples. All these contributions, and especially the novel framework may also have a clinical impact, as the overall medical care is gradually moving in the direction of a personalised one. By training a small number of doctors it may be possible for them to use the framework directly and find different sub-types of the disease they are investigating

A systematic review of the applications of Expert Systems (ES) and machine learning (ML) in clinical urology

Background: Testing a hypothesis for ‘factors-outcome effect’ is a common quest, but standard statistical regression analysis tools are rendered ineffective by data contaminated with too many noisy variables. Expert Systems (ES) can provide an alternative methodology in analysing data to identify variables with the highest correlation to the outcome. By applying their effective machine learning (ML) abilities, significant research time and costs can be saved. The study aims to systematically review the applications of ES in urological research and their methodological models for effective multi-variate analysis. Their domains, development and validity will be identified. Methods: The PRISMA methodology was applied to formulate an effective method for data gathering and analysis. This study search included seven most relevant information sources: WEB OF SCIENCE, EMBASE, BIOSIS CITATION INDEX, SCOPUS, PUBMED, Google Scholar and MEDLINE. Eligible articles were included if they applied one of the known ML models for a clear urological research question involving multivariate analysis. Only articles with pertinent research methods in ES models were included. The analysed data included the system model, applications, input/output variables, target user, validation, and outcomes. Both ML models and the variable analysis were comparatively reported for each system. Results: The search identified n = 1087 articles from all databases and n = 712 were eligible for examination against inclusion criteria. A total of 168 systems were finally included and systematically analysed demonstrating a recent increase in uptake of ES in academic urology in particular artificial neural networks with 31 systems. Most of the systems were applied in urological oncology (prostate cancer = 15, bladder cancer = 13) where diagnostic, prognostic and survival predictor markers were investigated. Due to the heterogeneity of models and their statistical tests, a meta-analysis was not feasible. Conclusion: ES utility offers an effective ML potential and their applications in research have demonstrated a valid model for multi-variate analysis. The complexity of their development can challenge their uptake in urological clinics whilst the limitation of the statistical tools in this domain has created a gap for further research studies. Integration of computer scientists in academic units has promoted the use of ES in clinical urological research

A comparison of three different methods for classification of breast cancer data

The classification of breast cancer patients is of great importance in cancer diagnosis. During the last few years, many algorithms have been proposed for this task. In this paper, we review different supervised machine learning techniques for classification of a novel dataset and perform a methodological comparison of these. We used the C4.5 tree classifier, a Multilayer Perceptron and a naïve Bayes classifier over a large set of tumour markers. We found good performance of the Multilayer Perceptron even when we reduced the number of features to be classified. We found naive Bayes achieved a competitive performance even though the assumption of normality of the data is strongly violated

Cancer profiles by affinity propagation

The affinity propagation algorithm is applied to a problem of breast cancer subtyping using traditional biologic markers. The algorithm provides a procedure to determine the number of profiles to be considered. A well know breast cancer case series was used to compare the results of the affinity propagation with the results obtained with standard algorithms and indexes for the optimal choice of the number of clusters. Results from affinity propagation are consistent with the results already obtained having the advantage of providing an indication about the number of clusters

Biomarker Clustering of Colorectal Cancer Data to Complement Clinical Classification

In this paper, we describe a dataset relating to cellular and physical conditions of patients who are operated upon to remove colorectal tumours. This data provides a unique insight into immunological status at the point of tumour removal, tumour classification and post-operative survival. Attempts are made to cluster this dataset and important subsets of it in an effort to characterize the data and validate existing standards for tumour classification. It is apparent from optimal clustering that existing tumour classification is largely unrelated to immunological factors within a patient and that there may be scope for re-evaluating treatment options and survival estimates based on a combination of tumour physiology and patient histochemistry.Comment: Federated Conference on Computer Science and Information Systems (FedCSIS), pp 187-191, 201

A "non-parametric" version of the naive Bayes classifier

Many algorithms have been proposed for the machine learning task of classication. One of the simplest methods, the naive Bayes classifyer, has often been found to give good performance despite the fact that its underlying assumptions (of independence and a Normal distribution of the variables) are perhaps violated. In previous work, we applied naive Bayes and other standard algorithms to a breast cancer database from Nottingham City Hospital in which the variables are highly non-Normal and found that the algorithm performed well when predicting a class that had been derived from the same data. However, when we then applied naive Bayes to predict an alternative clinical variable, it performed much worse than other techniques. This motivated us to propose an alternative method, based on naive Bayes, which removes the requirement for the variables to be Normally distributed, but retains the essential structure and other underlying assumptions of the method. We tested our novel algorithm on our breast cancer data and on three UCI datasets which also exhibited strong violations of Normality. We found our algorithm outperformed naive Bayes in all four cases and outperformed multinomial logistic regression (MLR) in two cases. We conclude that our method offers a competitive alternative to MLR and naive Bayes when dealing with data sets in which non-Normal distributions are observed

Attentional bias towards high and low caloric food on repeated visual food stimuli: An ERP study

Food variety influences appetitive behaviour, motivation to eat and energy intake. Research found that repeated exposure to varied food images increases the motivation towards food in adults and children. This study investigates the effects of repetition on the modulation of early and late components of event-related potentials (ERPs) when participants passively viewed the same food and non-food images repeatedly. The motivational attention to food and non-food images were assessed in frontal, centroparietal, parietooccipital and occipitotemporal areas of the brain. Participants showed increased late positive potential (late ERP component) to high caloric image in the occipitotemporal region compared to low caloric and nonfood images. Similar effects could be seen in the early ERP component in the frontal region, but with reversed polarity. Data suggest that both the early and late ERP components show greater ERP amplitude when viewing high caloric images than low caloric and non-food images. Despite repeated exposure to same image, high caloric food continued to show sustained attention compared to low caloric and non-food image