Statistical methods for tissue array images - algorithmic scoring and co-training

Recent advances in tissue microarray technology have allowed immunohistochemistry to become a powerful medium-to-high throughput analysis tool, particularly for the validation of diagnostic and prognostic biomarkers. However, as study size grows, the manual evaluation of these assays becomes a prohibitive limitation; it vastly reduces throughput and greatly increases variability and expense. We propose an algorithm - Tissue Array Co-Occurrence Matrix Analysis (TACOMA) - for quantifying cellular phenotypes based on textural regularity summarized by local inter-pixel relationships. The algorithm can be easily trained for any staining pattern, is absent of sensitive tuning parameters and has the ability to report salient pixels in an image that contribute to its score. Pathologists' input via informative training patches is an important aspect of the algorithm that allows the training for any specific marker or cell type. With co-training, the error rate of TACOMA can be reduced substantially for a very small training sample (e.g., with size 30). We give theoretical insights into the success of co-training via thinning of the feature set in a high-dimensional setting when there is "sufficient" redundancy among the features. TACOMA is flexible, transparent and provides a scoring process that can be evaluated with clarity and confidence. In a study based on an estrogen receptor (ER) marker, we show that TACOMA is comparable to, or outperforms, pathologists' performance in terms of accuracy and repeatability.Comment: Published in at http://dx.doi.org/10.1214/12-AOAS543 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Text authorship identified using the dynamics of word co-occurrence networks

The identification of authorship in disputed documents still requires human expertise, which is now unfeasible for many tasks owing to the large volumes of text and authors in practical applications. In this study, we introduce a methodology based on the dynamics of word co-occurrence networks representing written texts to classify a corpus of 80 texts by 8 authors. The texts were divided into sections with equal number of linguistic tokens, from which time series were created for 12 topological metrics. The series were proven to be stationary (p-value>0.05), which permits to use distribution moments as learning attributes. With an optimized supervised learning procedure using a Radial Basis Function Network, 68 out of 80 texts were correctly classified, i.e. a remarkable 85% author matching success rate. Therefore, fluctuations in purely dynamic network metrics were found to characterize authorship, thus opening the way for the description of texts in terms of small evolving networks. Moreover, the approach introduced allows for comparison of texts with diverse characteristics in a simple, fast fashion

Gene Expression Analysis Methods on Microarray Data a A Review

In recent years a new type of experiments are changing the way that biologists and other specialists analyze many problems. These are called high throughput experiments and the main difference with those that were performed some years ago is mainly in the quantity of the data obtained from them. Thanks to the technology known generically as microarrays, it is possible to study nowadays in a single experiment the behavior of all the genes of an organism under different conditions. The data generated by these experiments may consist from thousands to millions of variables and they pose many challenges to the scientists who have to analyze them. Many of these are of statistical nature and will be the center of this review. There are many types of microarrays which have been developed to answer different biological questions and some of them will be explained later. For the sake of simplicity we start with the most well known ones: expression microarrays

Credit Scoring Using Machine Learning

For financial institutions and the economy at large, the role of credit scoring in lending decisions cannot be overemphasised. An accurate and well-performing credit scorecard allows lenders to control their risk exposure through the selective allocation of credit based on the statistical analysis of historical customer data. This thesis identifies and investigates a number of specific challenges that occur during the development of credit scorecards. Four main contributions are made in this thesis. First, we examine the performance of a number supervised classification techniques on a collection of imbalanced credit scoring datasets. Class imbalance occurs when there are significantly fewer examples in one or more classes in a dataset compared to the remaining classes. We demonstrate that oversampling the minority class leads to no overall improvement to the best performing classifiers. We find that, in contrast, adjusting the threshold on classifier output yields, in many cases, an improvement in classification performance. Our second contribution investigates a particularly severe form of class imbalance, which, in credit scoring, is referred to as the low-default portfolio problem. To address this issue, we compare the performance of a number of semi-supervised classification algorithms with that of logistic regression. Based on the detailed comparison of classifier performance, we conclude that both approaches merit consideration when dealing with low-default portfolios. Third, we quantify the differences in classifier performance arising from various implementations of a real-world behavioural scoring dataset. Due to commercial sensitivities surrounding the use of behavioural scoring data, very few empirical studies which directly address this topic are published. This thesis describes the quantitative comparison of a range of dataset parameters impacting classification performance, including: (i) varying durations of historical customer behaviour for model training; (ii) different lengths of time from which a borrower’s class label is defined; and (iii) using alternative approaches to define a customer’s default status in behavioural scoring. Finally, this thesis demonstrates how artificial data may be used to overcome the difficulties associated with obtaining and using real-world data. The limitations of artificial data, in terms of its usefulness in evaluating classification performance, are also highlighted. In this work, we are interested in generating artificial data, for credit scoring, in the absence of any available real-world data

Biomarker discovery across annotated and unannotated microarray datasets using semi-supervised learning

The growing body of DNA microarray data has the potential to advance our understanding of the molecular basis of disease. However annotating microarray datasets with clinically useful information is not always possible, as this often requires access to detailed patient records. In this study we introduce GLAD, a new Semi-Supervised Learning (SSL) method for combining independent annotated datasets and unannotated datasets with the aim of identifying more robust sample classifiers

Automated interpretation of benthic stereo imagery

Autonomous benthic imaging, reduces human risk and increases the amount of collected data. However, manually interpreting these high volumes of data is onerous, time consuming and in many cases, infeasible. The objective of this thesis is to improve the scientific utility of the large image datasets. Fine-scale terrain complexity is typically quantified by rugosity and measured by divers using chains and tape measures. This thesis proposes a new technique for measuring terrain complexity from 3D stereo image reconstructions, which is non-contact and can be calculated at multiple scales over large spatial extents. Using robots, terrain complexity can be measured without endangering humans, beyond scuba depths. Results show that this approach is more robust, flexible and easily repeatable than traditional methods. These proposed terrain complexity features are combined with visual colour and texture descriptors and applied to classifying imagery. New multi-dataset feature selection methods are proposed for performing feature selection across multiple datasets, and are shown to improve the overall classification performance. The results show that the most informative predictors of benthic habitat types are the new terrain complexity measurements. This thesis presents a method that aims to reduce human labelling effort, while maximising classification performance by combining pre-clustering with active learning. The results support that utilising the structure of the unlabelled data in conjunction with uncertainty sampling can significantly reduce the number of labels required for a given level of accuracy. Typically 0.00001–0.00007% of image data is annotated and processed for science purposes (20–50 points in 1–2% of the images). This thesis proposes a framework that uses existing human-annotated point labels to train a superpixel-based automated classification system, which can extrapolate the classified results to every pixel across all the images of an entire survey

Automated interpretation of benthic stereo imagery

Autonomous benthic imaging, reduces human risk and increases the amount of collected data. However, manually interpreting these high volumes of data is onerous, time consuming and in many cases, infeasible. The objective of this thesis is to improve the scientific utility of the large image datasets. Fine-scale terrain complexity is typically quantified by rugosity and measured by divers using chains and tape measures. This thesis proposes a new technique for measuring terrain complexity from 3D stereo image reconstructions, which is non-contact and can be calculated at multiple scales over large spatial extents. Using robots, terrain complexity can be measured without endangering humans, beyond scuba depths. Results show that this approach is more robust, flexible and easily repeatable than traditional methods. These proposed terrain complexity features are combined with visual colour and texture descriptors and applied to classifying imagery. New multi-dataset feature selection methods are proposed for performing feature selection across multiple datasets, and are shown to improve the overall classification performance. The results show that the most informative predictors of benthic habitat types are the new terrain complexity measurements. This thesis presents a method that aims to reduce human labelling effort, while maximising classification performance by combining pre-clustering with active learning. The results support that utilising the structure of the unlabelled data in conjunction with uncertainty sampling can significantly reduce the number of labels required for a given level of accuracy. Typically 0.00001–0.00007% of image data is annotated and processed for science purposes (20–50 points in 1–2% of the images). This thesis proposes a framework that uses existing human-annotated point labels to train a superpixel-based automated classification system, which can extrapolate the classified results to every pixel across all the images of an entire survey

Features analysis for identification of date and party hubs in protein interaction network of Saccharomyces Cerevisiae

<p>Abstract</p> <p>Background</p> <p>It has been understood that biological networks have modular organizations which are the sources of their observed complexity. Analysis of networks and motifs has shown that two types of hubs, party hubs and date hubs, are responsible for this complexity. Party hubs are local coordinators because of their high co-expressions with their partners, whereas date hubs display low co-expressions and are assumed as global connectors. However there is no mutual agreement on these concepts in related literature with different studies reporting their results on different data sets. We investigated whether there is a relation between the biological features of <it>Saccharomyces Cerevisiae</it>'s proteins and their roles as non-hubs, intermediately connected, party hubs, and date hubs. We propose a classifier that separates these four classes.</p> <p>Results</p> <p>We extracted different biological characteristics including amino acid sequences, domain contents, repeated domains, functional categories, biological processes, cellular compartments, disordered regions, and position specific scoring matrix from various sources. Several classifiers are examined and the best feature-sets based on average correct classification rate and correlation coefficients of the results are selected. We show that fusion of five feature-sets including domains, Position Specific Scoring Matrix-400, cellular compartments level one, and composition pairs with two and one gaps provide the best discrimination with an average correct classification rate of 77%.</p> <p>Conclusions</p> <p>We study a variety of known biological feature-sets of the proteins and show that there is a relation between domains, Position Specific Scoring Matrix-400, cellular compartments level one, composition pairs with two and one gaps of <it>Saccharomyces Cerevisiae'</it>s proteins, and their roles in the protein interaction network as non-hubs, intermediately connected, party hubs and date hubs. This study also confirms the possibility of predicting non-hubs, party hubs and date hubs based on their biological features with acceptable accuracy. If such a hypothesis is correct for other species as well, similar methods can be applied to predict the roles of proteins in those species.</p