A scale space approach for unsupervised feature selection in mass spectra classification for ovarian cancer detection

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry spectra, widely used in proteomics studies as a screening tool for protein profiling and to detect discriminatory signals, are high dimensional data. A large number of local maxima (a.k.a. <it>peaks</it>) have to be analyzed as part of computational pipelines aimed at the realization of efficient predictive and screening protocols. With this kind of data dimensions and samples size the risk of over-fitting and selection bias is pervasive. Therefore the development of bio-informatics methods based on unsupervised feature extraction can lead to general tools which can be applied to several fields of predictive proteomics.</p> <p>Results</p> <p>We propose a method for feature selection and extraction grounded on the theory of multi-scale spaces for high resolution spectra derived from analysis of serum. Then we use support vector machines for classification. In particular we use a database containing 216 samples spectra divided in 115 cancer and 91 control samples. The overall accuracy averaged over a large cross validation study is 98.18. The area under the ROC curve of the best selected model is 0.9962.</p> <p>Conclusion</p> <p>We improved previous known results on the problem on the same data, with the advantage that the proposed method has an unsupervised feature selection phase. All the developed code, as MATLAB scripts, can be downloaded from <url>http://medeaserver.isa.cnr.it/dacierno/spectracode.htm</url></p

Comparison of feature selection and classification for MALDI-MS data

INTRODUCTION: In the classification of Mass Spectrometry (MS) proteomics data, peak detection, feature selection, and learning classifiers are critical to classification accuracy. To better understand which methods are more accurate when classifying data, some publicly available peak detection algorithms for Matrix assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS) data were recently compared; however, the issue of different feature selection methods and different classification models as they relate to classification performance has not been addressed. With the application of intelligent computing, much progress has been made in the development of feature selection methods and learning classifiers for the analysis of high-throughput biological data. The main objective of this paper is to compare the methods of feature selection and different learning classifiers when applied to MALDI-MS data and to provide a subsequent reference for the analysis of MS proteomics data. RESULTS: We compared a well-known method of feature selection, Support Vector Machine Recursive Feature Elimination (SVMRFE), and a recently developed method, Gradient based Leave-one-out Gene Selection (GLGS) that effectively performs microarray data analysis. We also compared several learning classifiers including K-Nearest Neighbor Classifier (KNNC), Naïve Bayes Classifier (NBC), Nearest Mean Scaled Classifier (NMSC), uncorrelated normal based quadratic Bayes Classifier recorded as UDC, Support Vector Machines, and a distance metric learning for Large Margin Nearest Neighbor classifier (LMNN) based on Mahanalobis distance. To compare, we conducted a comprehensive experimental study using three types of MALDI-MS data. CONCLUSION: Regarding feature selection, SVMRFE outperformed GLGS in classification. As for the learning classifiers, when classification models derived from the best training were compared, SVMs performed the best with respect to the expected testing accuracy. However, the distance metric learning LMNN outperformed SVMs and other classifiers on evaluating the best testing. In such cases, the optimum classification model based on LMNN is worth investigating for future study

Mass spectral imaging of clinical samples using deep learning

A better interpretation of tumour heterogeneity and variability is vital for the improvement of novel diagnostic techniques and personalized cancer treatments. Tumour tissue heterogeneity is characterized by biochemical heterogeneity, which can be investigated by unsupervised metabolomics. Mass Spectrometry Imaging (MSI) combined with Machine Learning techniques have generated increasing interest as analytical and diagnostic tools for the analysis of spatial molecular patterns in tissue samples. Considering the high complexity of data produced by the application of MSI, which can consist of many thousands of spectral peaks, statistical analysis and in particular machine learning and deep learning have been investigated as novel approaches to deduce the relationships between the measured molecular patterns and the local structural and biological properties of the tissues. Machine learning have historically been divided into two main categories: Supervised and Unsupervised learning. In MSI, supervised learning methods may be used to segment tissues into histologically relevant areas e.g. the classification of tissue regions in H&E (Haemotoxylin and Eosin) stained samples. Initial classification by an expert histopathologist, through visual inspection enables the development of univariate or multivariate models, based on tissue regions that have significantly up/down-regulated ions. However, complex data may result in underdetermined models, and alternative methods that can cope with high dimensionality and noisy data are required. Here, we describe, apply, and test a novel diagnostic procedure built using a combination of MSI and deep learning with the objective of delineating and identifying biochemical differences between cancerous and non-cancerous tissue in metastatic liver cancer and epithelial ovarian cancer. The workflow investigates the robustness of single (1D) to multidimensional (3D) tumour analyses and also highlights possible biomarkers which are not accessible from classical visual analysis of the H&E images. The identification of key molecular markers may provide a deeper understanding of tumour heterogeneity and potential targets for intervention.Open Acces

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Mass spectrometry data mining for cancer detection

Early detection of cancer is crucial for successful intervention strategies. Mass spectrometry-based high throughput proteomics is recognized as a major breakthrough in cancer detection. Many machine learning methods have been used to construct classifiers based on mass spectrometry data for discriminating between cancer stages, yet, the classifiers so constructed generally lack biological interpretability. To better assist clinical uses, a key step is to discover ”biomarker signature profiles”, i.e. combinations of a small number of protein biomarkers strongly discriminating between cancer states. This dissertation introduces two innovative algorithms to automatically search for a signature and to construct a high-performance signature-based classifier for cancer discrimination tasks based on mass spectrometry data, such as data acquired by MALDI or SELDI techniques. Our first algorithm assumes that homogeneous groups of mass spectra can be modeled by (unknown) Gibbs distributions to generate an optimal signature and an associated signature-based classifier by robust log-likelihood analysis; our second algorithm uses a stochastic optimization algorithm to search for two lists of biomarkers, and then constructs a signature-based classifier. To support these two algorithms theoretically, this dissertation also studies the empirical probability distributions of mass spectrometry data and implements the actual fitting of Markov random fields to these high-dimensional distributions. We have validated our two signature discovery algorithms on several mass spectrometry datasets related to ovarian cancer and to colorectal cancer patients groups. For these cancer discrimination tasks, our algorithms have yielded better classification performances than existing machine learning algorithms and in addition,have generated more interpretable explicit signatures.Mathematics, Department o

On consensus biomarker selection

<p>Abstract</p> <p>Background</p> <p>Recent development of mass spectrometry technology enabled the analysis of complex peptide mixtures. A lot of effort is currently devoted to the identification of biomarkers in human body fluids like serum or plasma, based on which new diagnostic tests for different diseases could be constructed. Various biomarker selection procedures have been exploited in recent studies. It has been noted that they often lead to different biomarker lists and as a consequence, the patient classification may also vary.</p> <p>Results</p> <p>Here we propose a new approach to the biomarker selection problem: to apply several competing feature ranking procedures and compute a consensus list of features based on their outcomes. We validate our methods on two proteomic datasets for the diagnosis of ovarian and prostate cancer.</p> <p>Conclusion</p> <p>The proposed methodology can improve the classification results and at the same time provide a unified biomarker list for further biological examinations and interpretation.</p

Feature Space Modeling for Accurate and Efficient Learning From Non-Stationary Data

A non-stationary dataset is one whose statistical properties such as the mean, variance, correlation, probability distribution, etc. change over a specific interval of time. On the contrary, a stationary dataset is one whose statistical properties remain constant over time. Apart from the volatile statistical properties, non-stationary data poses other challenges such as time and memory management due to the limitation of computational resources mostly caused by the recent advancements in data collection technologies which generate a variety of data at an alarming pace and volume. Additionally, when the collected data is complex, managing data complexity, emerging from its dimensionality and heterogeneity, can pose another challenge for effective computational learning. The problem is to enable accurate and efficient learning from non-stationary data in a continuous fashion over time while facing and managing the critical challenges of time, memory, concept change, and complexity simultaneously. Feature space modeling is one of the most effective solutions to address this problem. For non-stationary data, selecting relevant features is even more critical than stationary data due to the reduction of feature dimension which can ensure the best use a computational resource to produce higher accuracy and efficiency by data mining algorithms. In this dissertation, we investigated a variety of feature space modeling techniques to improve the overall performance of data mining algorithms. In particular, we built Relief based feature sub selection method in combination with data complexity iv analysis to improve the classification performance using ovarian cancer image data collected in a non-stationary batch mode. We also collected time series health sensor data in a streaming environment and deployed feature space transformation using Singular Value Decomposition (SVD). This led to reduced dimensionality of feature space resulting in better accuracy and efficiency produced by Density Ration Estimation Method in identifying potential change points in data over time. We have also built an unsupervised feature space modeling using matrix factorization and Lasso Regression which was successfully deployed in conjugate with Relative Density Ratio Estimation to address the botnet attacks in a non-stationary environment. Relief based feature model improved 16% accuracy of Fuzzy Forest classifier. For change detection framework, we observed 9% improvement in accuracy for PCA feature transformation. Due to the unsupervised feature selection model, for 2% and 5% malicious traffic ratio, the proposed botnet detection framework exhibited average 20% better accuracy than One Class Support Vector Machine (OSVM) and average 25% better accuracy than Autoencoder. All these results successfully demonstrate the effectives of these feature space models. The fundamental theme that repeats itself in this dissertation is about modeling efficient feature space to improve both accuracy and efficiency of selected data mining models. Every contribution in this dissertation has been subsequently and successfully employed to capitalize on those advantages to solve real-world problems. Our work bridges the concepts from multiple disciplines ineffective and surprising ways, leading to new insights, new frameworks, and ultimately to a cross-production of diverse fields like mathematics, statistics, and data mining