BMC Systems Biology

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BACKGROUND: Improving efficiency of disease diagnosis based on phenotype ontology is a critical yet challenging research area. Recently, Human Phenotype Ontology (HPO)-based semantic similarity has been affectively and widely used to identify causative genes and diseases. However, current phenotype similarity measurements just consider the annotations and hierarchy structure of HPO, neglecting the definition description of phenotype terms. RESULTS: In this paper, we propose a novel phenotype similarity measurement, termed as DisPheno, which adequately incorporates the definition of phenotype terms in addition to HPO structure and annotations to measure the similarity between phenotype terms...

BACKGROUND: Systematic fusion of multiple data sources for Gene Regulatory Networks (GRN) inference remains a key challenge in systems biology. We incorporate information from protein-protein interaction networks (PPIN) into the process of GRN inference from gene expression (GE) data. However, existing PPIN remain sparse and transitive protein interactions can help predict missing protein interactions. We therefore propose a systematic probabilistic framework on fusing GE data and transitive protein interaction data to coherently build GRN...

BACKGROUND: Single-cell RNA sequencing (scRNAseq) data always involves various unwanted variables, which would be able to mask the true signal to identify cell-types. More efficient way of dealing with this issue is to extract low dimension information from high dimensional gene expression data to represent cell-type structure. In the past two years, several powerful matrix factorization tools were developed for scRNAseq data, such as NMF, ZIFA, pCMF and ZINB-WaVE. But the existing approaches either are unable to directly model the raw count of scRNAseq data or are really time-consuming when handling a large number of cells (e...

BACKGROUND: The topological landscape of gene interaction networks provides a rich source of information for inferring functional patterns of genes or proteins. However, it is still a challenging task to aggregate heterogeneous biological information such as gene expression and gene interactions to achieve more accurate inference for prediction and discovery of new gene interactions. In particular, how to generate a unified vector representation to integrate diverse input data is a key challenge addressed here...

BACKGROUND: Biological experiments have confirmed the association between miRNAs and various diseases. However, such experiments are costly and time consuming. Computational methods help select potential disease-related miRNAs to improve the efficiency of biological experiments. METHODS: In this work, we develop a novel method using multiple types of data to calculate miRNA and disease similarity based on mutual information, and add miRNA family and cluster information to predict human disease-related miRNAs (FCMDAP)...

BACKGROUND: Anti-tumor necrosis factor alpha (TNF- α) therapy has made a significant impact on treating psoriasis. Despite these agents being designed to block TNF- α activity, their mechanism of action in the remission of psoriasis is still not fully understood at the molecular level. RESULTS: To better understand the molecular mechanisms of Anti-TNF- α therapy, we analysed the global gene expression profile (using mRNA microarray) in peripheral blood mononuclear cells (PBMCs) that were collected from 6 psoriasis patients before and 12 weeks after the treatment of etanercept...

BACKGROUND: Flow cytometry is a popular technology for quantitative single-cell profiling of cell surface markers. It enables expression measurement of tens of cell surface protein markers in millions of single cells. It is a powerful tool for discovering cell sub-populations and quantifying cell population heterogeneity. Traditionally, scientists use manual gating to identify cell types, but the process is subjective and is not effective for large multidimensional data. Many clustering algorithms have been developed to analyse these data but most of them are not scalable to very large data sets with more than ten million cells...

BACKGROUND: Major alteration in lifestyle of human population has promoted Type 2 diabetes mellitus (T2DM) to the level of an epidemic. This metabolic disorder is characterized by insulin resistance and pancreatic β-cell dysfunction and apoptosis, triggered by endoplasmic reticulum (ER) stress, oxidative stress and cytokines. Computational modeling is necessary to consolidate information from various sources in order to obtain a comprehensive understanding of the pathogenesis of T2DM and to investigate possible interventions by performing in silico simulations...

BACKGROUND: Characterization of drug-protein interaction networks with biological features has recently become challenging in recent pharmaceutical science toward a better understanding of polypharmacology. RESULTS: We present a novel method for systematic analyses of the underlying features characteristic of drug-protein interaction networks, which we call "drug-protein interaction signatures" from the integration of large-scale heterogeneous data of drugs and proteins...

BACKGROUND: Identification of Hürthle cell cancers by non-operative fine-needle aspiration biopsy (FNAB) of thyroid nodules is challenging. Resultingly, non-cancerous Hürthle lesions were conventionally distinguished from Hürthle cell cancers by histopathological examination of tissue following surgical resection. Reliance on histopathological evaluation requires patients to undergo surgery to obtain a diagnosis despite most being non-cancerous. It is highly desirable to avoid surgery and to provide accurate classification of benignity versus malignancy from FNAB preoperatively...

BACKGROUND: Numerous experimental results have indicated that microRNAs (miRNAs) play a vital role in biological processes, as well as outbreaks of diseases at the molecular level. Despite their important role in biological processes, knowledge regarding specific functions of miRNAs in the development of human diseases is very limited. While attempting to solve this problem, many computational approaches have been proposed and attracted significant attention. However, most previous approaches suffer from the common problem of being inapplicable to new diseases without any known miRNA-disease associations...

BACKGROUND: Adaptation and homeostasis are basic features of information processing in cells and seen in a broad range of contexts. Much of the current understanding of adaptation in network modules/motifs is based on their response to simple stimuli. Recently, there have also been studies of adaptation in dynamic stimuli. However a broader synthesis of how different circuits of adaptation function, and which circuits enable a broader adaptive behaviour in classes of more complex and spatial stimuli is largely missing...

BACKGROUND: One of the questions in the design of cancer clinical trials with combination of two drugs is in which order to administer the drugs. This is an important question, especially in the case where one agent may interfere with the effectiveness of the other agent. RESULTS: In the present paper we develop a mathematical model to address this scheduling question in a specific case where one of the drugs is anti-VEGF, which is known to affect the perfusion of other drugs...

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BACKGROUND: The JAK/STAT signaling pathway is involved in many aging-related cellular functions. However, effects of overexpression of genes controlling JAK/STAT signal transduction on longevity of model organisms have not been studied. Here we evaluate the effect of overexpression of the unpaired 1 (upd1) gene, which encodes an activating ligand for JAK/STAT pathway, on the lifespan of Drosophila melanogaster. RESULTS: Overexpression of upd1 in the intestine caused a pronounced shortening of the median lifespan by 54...

BACKGROUND: A cancer cell line originating from human epithelial colorectal adenocarcinoma (Caco-2 cells) serves as a high capacity model for a preclinical screening of drugs. Recent need for incorporating barrier tissue into multi-organ chips calls for inclusion of Caco-2 cells into microperfused environment. RESULTS: This article describes a series of systems biology insights obtained from comparing Caco-2 models cells grown as conventional 2D layer and in a microfluidic chip...

BACKGROUND: The strategy of adaptation of the human body in microgravity is largely associated with the plasticity of cardiovascular system regulatory mechanisms. During long-term space flights the changes in the stroke volume of the heart are observed, the heart rate decreases, the phase structure of cardiac cycle is readjusted The purpose of this work was to clarify urine proteome changes associated with the initial condition of the heart rate autonomic regulation mechanisms in cosmonauts who have participated in long space missions...

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BACKGROUND: Microscopic images are widely used in plant biology as an essential source of information on morphometric characteristics of the cells and the topological characteristics of cellular tissue pattern due to modern computer vision algorithms. High-resolution 3D confocal images allow extracting quantitative characteristics describing the cell structure of leaf epidermis. For some issues in the study of cereal leaves development, it is required to apply the staining techniques with fluorescent dyes and to scan rather large fragments consisting of several frames...