Dimensionality reduction methods for microarray cancer data using prior knowledge

Microarray studies are currently a very popular source of biological information. They allow the simultaneous measurement of hundreds of thousands of genes, drastically increasing the amount of data that can be gathered in a small amount of time and also decreasing the cost of producing such results. Large numbers of high dimensional data sets are currently being generated and there is an ongoing need to find ways to analyse them to obtain meaningful interpretations. Many microarray experiments are concerned with answering specific biological or medical questions regarding diseases and treatments. Cancer is one of the most popular research areas and there is a plethora of data available requiring in depth analysis. Although the analysis of microarray data has been thoroughly researched over the past ten years, new approaches still appear regularly, and may lead to a better understanding of the available information. The size of the modern data sets presents considerable difficulties to traditional methodologies based on hypothesis testing, and there is a new move towards the use of machine learning in microarray data analysis. Two new methods of using prior genetic knowledge in machine learning algorithms have been developed and their results are compared with existing methods. The prior knowledge consists of biological pathway data that can be found in on-line databases, and gene ontology terms. The first method, called ``a priori manifold learning'' uses the prior knowledge when constructing a manifold for non-linear feature extraction. It was found to perform better than both linear principal components analysis (PCA) and the non-linear Isomap algorithm (without prior knowledge) in both classification accuracy and quality of the clusters. Both pathway and GO terms were used as prior knowledge, and results showed that using GO terms can make the models over-fit the data. In the cases where the use of GO terms does not over-fit, the results are better than PCA, Isomap and a priori manifold learning using pathways. The second method, called ``the feature selection over pathway segmentation algorithm'', uses the pathway information to split a big dataset into smaller ones. Then, using AdaBoost, decision trees are constructed for each of the smaller sets and the sets that achieve higher classification accuracy are identified. The individual genes in these subsets are assessed to determine their role in the classification process. Using data sets concerning chronic myeloid leukaemia (CML) two subsets based on pathways were found to be strongly associated with the response to treatment. Using a different data set from measurements on lower grade glioma (LGG) tumours, four informative gene sets were discovered. Further analysis based on the Gini importance measure identified a set of genes for each cancer type (CML, LGG) that could predict the response to treatment very accurately (> 90%). Moreover a single gene that can predict the response to CML treatment accurately was identified.Open Acces