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

Multimodal Data Fusion and Quantitative Analysis for Medical Applications

Medical big data is not only enormous in its size, but also heterogeneous and complex in its data structure, which makes conventional systems or algorithms difficult to process. These heterogeneous medical data include imaging data (e.g., Positron Emission Tomography (PET), Computerized Tomography (CT), Magnetic Resonance Imaging (MRI)), and non-imaging data (e.g., laboratory biomarkers, electronic medical records, and hand-written doctor notes). Multimodal data fusion is an emerging vital field to address this urgent challenge, aiming to process and analyze the complex, diverse and heterogeneous multimodal data. The fusion algorithms bring great potential in medical data analysis, by 1) taking advantage of complementary information from different sources (such as functional-structural complementarity of PET/CT images) and 2) exploiting consensus information that reflects the intrinsic essence (such as the genetic essence underlying medical imaging and clinical symptoms). Thus, multimodal data fusion benefits a wide range of quantitative medical applications, including personalized patient care, more optimal medical operation plan, and preventive public health. Though there has been extensive research on computational approaches for multimodal fusion, there are three major challenges of multimodal data fusion in quantitative medical applications, which are summarized as feature-level fusion, information-level fusion and knowledge-level fusion: • Feature-level fusion. The first challenge is to mine multimodal biomarkers from high-dimensional small-sample multimodal medical datasets, which hinders the effective discovery of informative multimodal biomarkers. Specifically, efficient dimension reduction algorithms are required to alleviate "curse of dimensionality" problem and address the criteria for discovering interpretable, relevant, non-redundant and generalizable multimodal biomarkers. • Information-level fusion. The second challenge is to exploit and interpret inter-modal and intra-modal information for precise clinical decisions. Although radiomics and multi-branch deep learning have been used for implicit information fusion guided with supervision of the labels, there is a lack of methods to explicitly explore inter-modal relationships in medical applications. Unsupervised multimodal learning is able to mine inter-modal relationship as well as reduce the usage of labor-intensive data and explore potential undiscovered biomarkers; however, mining discriminative information without label supervision is an upcoming challenge. Furthermore, the interpretation of complex non-linear cross-modal associations, especially in deep multimodal learning, is another critical challenge in information-level fusion, which hinders the exploration of multimodal interaction in disease mechanism. • Knowledge-level fusion. The third challenge is quantitative knowledge distillation from multi-focus regions on medical imaging. Although characterizing imaging features from single lesions using either feature engineering or deep learning methods have been investigated in recent years, both methods neglect the importance of inter-region spatial relationships. Thus, a topological profiling tool for multi-focus regions is in high demand, which is yet missing in current feature engineering and deep learning methods. Furthermore, incorporating domain knowledge with distilled knowledge from multi-focus regions is another challenge in knowledge-level fusion. To address the three challenges in multimodal data fusion, this thesis provides a multi-level fusion framework for multimodal biomarker mining, multimodal deep learning, and knowledge distillation from multi-focus regions. Specifically, our major contributions in this thesis include: • To address the challenges in feature-level fusion, we propose an Integrative Multimodal Biomarker Mining framework to select interpretable, relevant, non-redundant and generalizable multimodal biomarkers from high-dimensional small-sample imaging and non-imaging data for diagnostic and prognostic applications. The feature selection criteria including representativeness, robustness, discriminability, and non-redundancy are exploited by consensus clustering, Wilcoxon filter, sequential forward selection, and correlation analysis, respectively. SHapley Additive exPlanations (SHAP) method and nomogram are employed to further enhance feature interpretability in machine learning models. • To address the challenges in information-level fusion, we propose an Interpretable Deep Correlational Fusion framework, based on canonical correlation analysis (CCA) for 1) cohesive multimodal fusion of medical imaging and non-imaging data, and 2) interpretation of complex non-linear cross-modal associations. Specifically, two novel loss functions are proposed to optimize the discovery of informative multimodal representations in both supervised and unsupervised deep learning, by jointly learning inter-modal consensus and intra-modal discriminative information. An interpretation module is proposed to decipher the complex non-linear cross-modal association by leveraging interpretation methods in both deep learning and multimodal consensus learning. • To address the challenges in knowledge-level fusion, we proposed a Dynamic Topological Analysis framework, based on persistent homology, for knowledge distillation from inter-connected multi-focus regions in medical imaging and incorporation of domain knowledge. Different from conventional feature engineering and deep learning, our DTA framework is able to explicitly quantify inter-region topological relationships, including global-level geometric structure and community-level clusters. K-simplex Community Graph is proposed to construct the dynamic community graph for representing community-level multi-scale graph structure. The constructed dynamic graph is subsequently tracked with a novel Decomposed Persistence algorithm. Domain knowledge is incorporated into the Adaptive Community Profile, summarizing the tracked multi-scale community topology with additional customizable clinically important factors

Spatio-Temporal Human Action Recognition Model using Deep Learning Techniques

Two-stream human recognition achieved great success in the development of video action recognition using deep learning. Recently many studies have shown that two-stream action recognition is a powerful feature extractor. The main contribution in this work is to develop a two-stream model based on spatial and temporal networks using convolutional neural networks with a convolution long-short term memory. The two-stream model with ImageNet pre-trained weights is used to retrieve spatial and temporal features. Output feature maps of the two-stream model are fused using sum fusion and fed as input to convolutional long-short-term memory. SoftMax function is used to get the final classification score. To avoid overfitting, we have adopted the data augmentation techniques. Finally, we demonstrated that the proposed model performs well in comparison to state-of-the-art two-stream models with an accuracy of 96.1% on UCF 101 dataset and 70.9% accuracy on the HMDB dataset

Rumor Detection on Social Media: Datasets, Methods and Opportunities

Social media platforms have been used for information and news gathering, and they are very valuable in many applications. However, they also lead to the spreading of rumors and fake news. Many efforts have been taken to detect and debunk rumors on social media by analyzing their content and social context using machine learning techniques. This paper gives an overview of the recent studies in the rumor detection field. It provides a comprehensive list of datasets used for rumor detection, and reviews the important studies based on what types of information they exploit and the approaches they take. And more importantly, we also present several new directions for future research.Comment: 10 page

Wireless Data Acquisition for Edge Learning: Data-Importance Aware Retransmission

By deploying machine-learning algorithms at the network edge, edge learning can leverage the enormous real-time data generated by billions of mobile devices to train AI models, which enable intelligent mobile applications. In this emerging research area, one key direction is to efficiently utilize radio resources for wireless data acquisition to minimize the latency of executing a learning task at an edge server. Along this direction, we consider the specific problem of retransmission decision in each communication round to ensure both reliability and quantity of those training data for accelerating model convergence. To solve the problem, a new retransmission protocol called data-importance aware automatic-repeat-request (importance ARQ) is proposed. Unlike the classic ARQ focusing merely on reliability, importance ARQ selectively retransmits a data sample based on its uncertainty which helps learning and can be measured using the model under training. Underpinning the proposed protocol is a derived elegant communication-learning relation between two corresponding metrics, i.e., signal-to-noise ratio (SNR) and data uncertainty. This relation facilitates the design of a simple threshold based policy for importance ARQ. The policy is first derived based on the classic classifier model of support vector machine (SVM), where the uncertainty of a data sample is measured by its distance to the decision boundary. The policy is then extended to the more complex model of convolutional neural networks (CNN) where data uncertainty is measured by entropy. Extensive experiments have been conducted for both the SVM and CNN using real datasets with balanced and imbalanced distributions. Experimental results demonstrate that importance ARQ effectively copes with channel fading and noise in wireless data acquisition to achieve faster model convergence than the conventional channel-aware ARQ.Comment: This is an updated version: 1) extension to general classifiers; 2) consideration of imbalanced classification in the experiments. Submitted to IEEE Journal for possible publicatio

Multimodal non-linear latent semantic method for information retrieval

La búsqueda y recuperación de datos multimodales es una importante tarea dentro del campo de búsqueda y recuperación de información, donde las consultas y los elementos de la base de datos objetivo están representados por un conjunto de modalidades, donde cada una de ellas captura un aspecto de un fenómeno de interés. Cada modalidad contiene información complementaria y común a otras modalidades. Con el fin de tomar ventaja de la información adicional distribuida a través de las distintas modalidades han sido desarrollados muchos algoritmos y métodos que utilizan las propiedades estadísticas en los datos multimodales para encontrar correlaciones implícitas, otros aprenden a calcular distancias heterogéneas, otros métodos aprenden a proyectar los datos desde el espacio de entrada hasta un espacio semántico común, donde las diferentes modalidades son comparables y se puede construir un ranking a partir de ellas. En esta tesis se presenta el diseño de un sistema para la búsqueda y recuperación de información multimodal que aprende varias proyecciones no lineales a espacios semánticos latentes donde las distintas modalidades son representadas en conjunto y es posible realizar comparaciones y medidas de similitud para construir rankings multimodales. Adicionalmente se propone un método kernelizado para la proyección de datos a un espacio semántico latente usando la información de las etiquetas como método de supervisión para construir índice multimodal que integra los datos multimodales y la información de las etiquetas; este método puede proyectar los datos a tres diferentes espacios semánticos donde varias configuraciones de búsqueda y recuperación de información pueden ser aplicadas. El sistema y el método propuestos fueron evaluados en un conjunto de datos compuesto por casos médicos, donde cada caso consta de una imagen de tejido prostático, un reporte de texto del patólogo y un valor de Gleason score como etiqueta de supervisión. Combinando la información multimodal y la información en las etiquetas se generó un índice multimodal que se utilizó para realizar la tarea de búsqueda y recuperación de información por contenido obteniendo resultados sobresalientes. Las proyecciones no-lineales permiten al modelo una mayor flexibilidad y capacidad de representación. Sin embargo calcular estas proyecciones no-lineales en un conjunto de datos enorme es computacionalmente costoso, para reducir este costo y habilitar el modelo para procesar datos a gran escala, la técnica del budget fue utilizada, mostrando un buen compromiso entre efectividad y velocidad.Multimodal information retrieval is an information retrieval sub-task where queries and database target elements are composed of several modalities or views. A modality is a representation of complex phenomena, captured and measured by different sensors or information sources, each one encodes some information about it. Each modality representation contains complementary and shared information about the phenomenon of interest, this additional information can be used to improve the information retrieval process. Several methods have been developed to take advantage of additional information distributed across different modalities. Some of them exploit statistical properties in multimodal data to find correlations and implicit relationships, others learn heterogeneous distance functions, and others learn linear and non-linear projections that transform data from the original input space to a common latent semantic space where different modalities are comparable. In spite of the attention dedicated to this issue, multimodal information retrieval is still an open problem. This thesis presents a multimodal information retrieval system designed to learn several mapping functions to transform multimodal data to a latent semantic space, where different modalities are combined and can be compared to build a multimodal ranking and perform a multimodal information retrieval task. Additionally, a multimodal kernelized latent semantic embedding method is proposed to construct a supervised multimodal index, integrating multimodal data and label supervision. This method can perform mappings to three different spaces where some information retrieval task setups can be performed. The proposed system and method were evaluated in a multimodal medical case-based retrieval task where data is composed of whole-slide images of prostate tissue samples, pathologist’s text report and Gleason score as a supervised label. Multimodal data and labels were combined to produce a multimodal index. This index was used to retrieve multimodal information and achieves outstanding results compared with previous works on this topic. Non-linear mappings provide more flexibility and representation capacity to the proposed model. However, constructing the non-linear mapping in a large dataset using kernel methods can be computationally costly. To reduce the cost and allow large scale applications, the budget technique was introduced, showing good performance between speed and effectiveness.COLCIENCIASJóvenes investigadores 761/2016Línea de investigación: Ciencias de la computaciónMaestrí