A flexible framework for sparse simultaneous component based data integration

<p>Abstract</p> <p>1 Background</p> <p>High throughput data are complex and methods that reveal structure underlying the data are most useful. Principal component analysis, frequently implemented as a singular value decomposition, is a popular technique in this respect. Nowadays often the challenge is to reveal structure in several sources of information (e.g., transcriptomics, proteomics) that are available for the same biological entities under study. Simultaneous component methods are most promising in this respect. However, the interpretation of the principal and simultaneous components is often daunting because contributions of each of the biomolecules (transcripts, proteins) have to be taken into account.</p> <p>2 Results</p> <p>We propose a sparse simultaneous component method that makes many of the parameters redundant by shrinking them to zero. It includes principal component analysis, sparse principal component analysis, and ordinary simultaneous component analysis as special cases. Several penalties can be tuned that account in different ways for the block structure present in the integrated data. This yields known sparse approaches as the lasso, the ridge penalty, the elastic net, the group lasso, sparse group lasso, and elitist lasso. In addition, the algorithmic results can be easily transposed to the context of regression. Metabolomics data obtained with two measurement platforms for the same set of <it>Escherichia coli </it>samples are used to illustrate the proposed methodology and the properties of different penalties with respect to sparseness across and within data blocks.</p> <p>3 Conclusion</p> <p>Sparse simultaneous component analysis is a useful method for data integration: First, simultaneous analyses of multiple blocks offer advantages over sequential and separate analyses and second, interpretation of the results is highly facilitated by their sparseness. The approach offered is flexible and allows to take the block structure in different ways into account. As such, structures can be found that are exclusively tied to one data platform (group lasso approach) as well as structures that involve all data platforms (Elitist lasso approach).</p> <p>4 Availability</p> <p>The additional file contains a MATLAB implementation of the sparse simultaneous component method.</p

Telomerase Inhibition Targets Clonogenic Multiple Myeloma Cells through Telomere Length-Dependent and Independent Mechanisms

Plasma cells constitute the majority of tumor cells in multiple myeloma (MM) but lack the potential for sustained clonogenic growth. In contrast, clonotypic B cells can engraft and recapitulate disease in immunodeficient mice suggesting they serve as the MM cancer stem cell (CSC). These tumor initiating B cells also share functional features with normal stem cells such as drug resistance and self-renewal potential. Therefore, the cellular processes that regulate normal stem cells may serve as therapeutic targets in MM. Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC. Moreover, we carried out both long and short-term inhibition studies to examine telomere length-dependent and independent activities.Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. In addition to these relatively long-term effects, 72 hours of imetelstat treatment inhibited clonogenic growth that was associated with MM CSC differentiation based on expression of the plasma cell antigen CD138 and the stem cell marker aldehyde dehydrogenase. Short-term treatment of MM CSC also decreased the expression of genes typically expressed by stem cells (OCT3/4, SOX2, NANOG, and BMI1) as revealed by quantitative real-time PCR.Telomerase activity regulates the clonogenic growth of MM CSC. Moreover, reductions in MM growth following both long and short-term telomerase inhibition suggest that it impacts CSC through telomere length-dependent and independent mechanisms

Key mechanisms governing resolution of lung inflammation

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered

Towards Automated Diagnosis with Attentive Multi-modal Learning Using Electronic Health Records and Chest X-Rays

Jointly learning from Electronic Health Records (EHR) and medical images is a promising area of research in deep learning for medical imaging. Using the context available in EHR together with medical images can lead to more efficient data usage. Recent work has shown that jointly learning from EHR and medical images can indeed improve performance on several tasks. Current methods are however still not independent of clinician input. To obtain an automated method only prior patient information should be used together with a medical image, without the reliance on further clinician input. In this paper we propose an automated multi-modal method which creates a joint feature representation based on prior patient information from EHR and associated X-ray scan. This feature representation, which joins the two different modalities through attention leverages the contextual relationship between the modalities. This method is used to perform two tasks: diagnosis classification and free-text diagnosis generation. We show the benefit of the multi-modal approach over single-modality approaches on both tasks

Long-short term memory network for RNA structure profiling super-resolution

Profiling of RNAs improves understanding of cellular mechanisms, which can be essential to cure various diseases. It is estimated to take years to fully characterize the three-dimensional structure of around 200,000 RNAs in human using the mutate-and-map strategy. In order to speed up the profiling process, we propose a solution based on super-resolution. We applied five machine learning regression methods to perform RNA structure profiling super-resolution, i.e. to recover the whole data sets using self-similarity in low-resolution (undersampled) data sets. In particular, our novel Interaction Encoded Long-Short Term Memory (IELSTM) network can handle multiple distant interactions in the RNA sequences. When compared with ridge regression, LASSO regression, multilayer perceptron regression, and random forest regression, IELSTM network can reduce the mean squared error and the median absolute error by at least 33% and 31% respectively in three RNA structure profiling data sets

Interactive deep metric learning for healthcare cohort discovery

© Springer Nature Singapore Pte Ltd. 2019. Given the continuous growth of large-scale complex electronic healthcare data, a data-driven healthcare cohort discovery facilitated by machine learning tools with domain expert knowledge is required to gain further insights of the healthcare system. Specifically, clustering plays a crucial role in healthcare cohort discovery, and metric learning is able to incorporate expert feedback to generate more fit-for-purpose clustering outputs. However, most of the existing metric learning methods assume all labelled instances already pre-exists, which is not always true in real-world applications. In addition, big data in healthcare also brings new challenges to metric learning on handling complex structured data. In this paper, we propose a novel systematic method, namely Interactive Deep Metric Learning (IDML), which uses an interactive process to iteratively incorporate feedback from domain experts to identify cohorts that are more relevant to a particular pre-defined purpose. Moreover, the proposed method leverages powerful deep learning-based embedding techniques to incrementally gain effective representations for the complex structures inherit in patient journey data. We experimentally evaluate the effectiveness of the proposed IDML using two public healthcare datasets. The proposed method has also been implemented into an interactive cohort discovery tool for a real-world application in healthcare