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

A Comparative Study of Pairwise Learning Methods based on Kernel Ridge Regression

Many machine learning problems can be formulated as predicting labels for a pair of objects. Problems of that kind are often referred to as pairwise learning, dyadic prediction or network inference problems. During the last decade kernel methods have played a dominant role in pairwise learning. They still obtain a state-of-the-art predictive performance, but a theoretical analysis of their behavior has been underexplored in the machine learning literature. In this work we review and unify existing kernel-based algorithms that are commonly used in different pairwise learning settings, ranging from matrix filtering to zero-shot learning. To this end, we focus on closed-form efficient instantiations of Kronecker kernel ridge regression. We show that independent task kernel ridge regression, two-step kernel ridge regression and a linear matrix filter arise naturally as a special case of Kronecker kernel ridge regression, implying that all these methods implicitly minimize a squared loss. In addition, we analyze universality, consistency and spectral filtering properties. Our theoretical results provide valuable insights in assessing the advantages and limitations of existing pairwise learning methods.Comment: arXiv admin note: text overlap with arXiv:1606.0427

Machine Learning for Multiclass Classification and Prediction of Alzheimer\u27s Disease

Alzheimer\u27s disease (AD) is an irreversible neurodegenerative disorder and a common form of dementia. This research aims to develop machine learning algorithms that diagnose and predict the progression of AD from multimodal heterogonous biomarkers with a focus placed on the early diagnosis. To meet this goal, several machine learning-based methods with their unique characteristics for feature extraction and automated classification, prediction, and visualization have been developed to discern subtle progression trends and predict the trajectory of disease progression. The methodology envisioned aims to enhance both the multiclass classification accuracy and prediction outcomes by effectively modeling the interplay between the multimodal biomarkers, handle the missing data challenge, and adequately extract all the relevant features that will be fed into the machine learning framework, all in order to understand the subtle changes that happen in the different stages of the disease. This research will also investigate the notion of multitasking to discover how the two processes of multiclass classification and prediction relate to one another in terms of the features they share and whether they could learn from one another for optimizing multiclass classification and prediction accuracy. This research work also delves into predicting cognitive scores of specific tests over time, using multimodal longitudinal data. The intent is to augment our prospects for analyzing the interplay between the different multimodal features used in the input space to the predicted cognitive scores. Moreover, the power of modality fusion, kernelization, and tensorization have also been investigated to efficiently extract important features hidden in the lower-dimensional feature space without being distracted by those deemed as irrelevant. With the adage that a picture is worth a thousand words, this dissertation introduces a unique color-coded visualization system with a fully integrated machine learning model for the enhanced diagnosis and prognosis of Alzheimer\u27s disease. The incentive here is to show that through visualization, the challenges imposed by both the variability and interrelatedness of the multimodal features could be overcome. Ultimately, this form of visualization via machine learning informs on the challenges faced with multiclass classification and adds insight into the decision-making process for a diagnosis and prognosis

Combining Molecular, Imaging, and Clinical Data Analysis for Predicting Cancer Prognosis

Cancer is one of the most detrimental diseases globally. Accordingly, the prognosis prediction of cancer patients has become a field of interest. In this review, we have gathered 43 stateof- the-art scientific papers published in the last 6 years that built cancer prognosis predictive models using multimodal data. We have defined the multimodality of data as four main types: clinical, anatomopathological, molecular, and medical imaging; and we have expanded on the information that each modality provides. The 43 studies were divided into three categories based on the modelling approach taken, and their characteristics were further discussed together with current issues and future trends. Research in this area has evolved from survival analysis through statistical modelling using mainly clinical and anatomopathological data to the prediction of cancer prognosis through a multi-faceted data-driven approach by the integration of complex, multimodal, and high-dimensional data containing multi-omics and medical imaging information and by applying Machine Learning and, more recently, Deep Learning techniques. This review concludes that cancer prognosis predictive multimodal models are capable of better stratifying patients, which can improve clinical management and contribute to the implementation of personalised medicine as well as provide new and valuable knowledge on cancer biology and its progression

Aplicaciones de las redes neuronales y el deep learning a la ingeniería biomédica

Nowadays, artificial neural networks and deep learning, are two of the most powerful machine learning tools, which aim to develop systems that learn automatically, recognize patterns, predict behaviors and generalize information from data sets. These two tools have become a potential field of research with applications to engineering, with biomedical engineering not being the exception. This article presents an updated review of the main applications of neural networks and deep learning in the areas of omics, imaging, brain-machine and body-machine interfaces, and the management and administration of public health; these areas extend from the study of processes at molecular level, to processes that involve large populations.Hoy en día, las redes neuronales artificiales y el deep learning, son dos de las herramientas más poderosas del aprendizaje de máquina, que tienen por objetivo desarrollar sistemas que aprenden automáticamente, reconocen patrones, predicen comportamientos y generalizan información a partir de conjuntos de datos.  Estas dos herramientas se han convertido en un potencial campo de investigación con aplicaciones a la ingeniería, no siendo la ingeniería biomédica la excepción. En este artículo se presenta una revisión actualizada de las principales aplicaciones de las redes neuronales y el deep learning a la ingeniería biomédica en las ramas de la ómica, la imagenología, las interfaces cerebro-máquina y hombre-máquina, y la gestión y administración de la salud pública; ramas que se extienden desde el estudio de procesos a nivel molecular, hasta procesos que involucran grandes poblaciones

Learning with Low-Quality Data: Multi-View Semi-Supervised Learning with Missing Views

The focus of this thesis is on learning approaches for what we call ``low-quality data'' and in particular data in which only small amounts of labeled target data is available. The first part provides background discussion on low-quality data issues, followed by preliminary study in this area. The remainder of the thesis focuses on a particular scenario: multi-view semi-supervised learning. Multi-view learning generally refers to the case of learning with data that has multiple natural views, or sets of features, associated with it. Multi-view semi-supervised learning methods try to exploit the combination of multiple views along with large amounts of unlabeled data in order to learn better predictive functions when limited labeled data is available. However, lack of complete view data limits the applicability of multi-view semi-supervised learning to real world data. Commonly, one data view is readily and cheaply available, but additionally views may be costly or only available in some cases. This thesis work aims to make multi-view semi-supervised learning approaches more applicable to real world data specifically by addressing the issue of missing views through both feature generation and active learning, and addressing the issue of model selection for semi-supervised learning with limited labeled data. This thesis introduces a unified approach for handling missing view data in multi-view semi-supervised learning tasks, which applies to both data with completely missing additional views and data only missing views in some instances. The idea is to learn a feature generation function mapping one view to another with the mapping biased to encourage the features generated to be useful for multi-view semi-supervised learning algorithms. The mapping is then used to fill in views as pre-processing. Unlike previously proposed single-view multi-view learning approaches, the proposed approach is able to take advantage of additional view data when available, and for the case of partial view presence is the first feature-generation approach specifically designed to take into account the multi-view semi-supervised learning aspect. The next component of this thesis is the analysis of an active view completion scenario. In some tasks, it is possible to obtain missing view data for a particular instance, but with some associated cost. Recent work has shown an active selection strategy can be more effective than a random one. In this thesis, a better understanding of active approaches is sought, and it is demonstrated that the effectiveness of an active selection strategy over a random one can depend on the relationship between the views. Finally, an important component of making multi-view semi-supervised learning applicable to real world data is the task of model selection, an open problem which is often avoided entirely in previous work. For cases of very limited labeled training data the commonly used cross-validation approach can become ineffective. This thesis introduces a re-training alternative to the method-dependent approaches similar in motivation to cross-validation, that involves generating new training and test data by sampling from the large amount of unlabeled data and estimated conditional probabilities for the labels. The proposed approaches are evaluated on a variety of multi-view semi-supervised learning data sets, and the experimental results demonstrate their efficacy

Systems Analytics and Integration of Big Omics Data

A “genotype"" is essentially an organism's full hereditary information which is obtained from its parents. A ""phenotype"" is an organism's actual observed physical and behavioral properties. These may include traits such as morphology, size, height, eye color, metabolism, etc. One of the pressing challenges in computational and systems biology is genotype-to-phenotype prediction. This is challenging given the amount of data generated by modern Omics technologies. This “Big Data” is so large and complex that traditional data processing applications are not up to the task. Challenges arise in collection, analysis, mining, sharing, transfer, visualization, archiving, and integration of these data. In this Special Issue, there is a focus on the systems-level analysis of Omics data, recent developments in gene ontology annotation, and advances in biological pathways and network biology. The integration of Omics data with clinical and biomedical data using machine learning is explored. This Special Issue covers new methodologies in the context of gene–environment interactions, tissue-specific gene expression, and how external factors or host genetics impact the microbiome