Modelling cancer progression using Mutual Hazard Networks.
Ontology highlight
ABSTRACT:
SUBMITTER: Schill R
PROVIDER: S-EPMC6956791 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Stock correlation networks use stock price data to explore the relationship between different stocks listed in the stock market. Currently this relationship is dominantly measured by the Pearson correlation coefficient. However, financial data suggest that nonlinear relationships may exist in the stock prices of different shares. To address this issue, this work uses mutual information to characterize the nonlinear relationship between stocks. Using 280 stocks traded at the Shanghai Stocks Exchange in China during the period of 2014-2016, we first compare the effectiveness of the correlation coefficient and mutual information for measuring stock relationships. Based on these two measures, we then develop two stock networks using the Minimum Spanning Tree method and study the topological properties of these networks, including degree, path length and the power-law distribution. The relationship network based on mutual information has a better distribution of the degree and larger value of the power-law distribution than those using the correlation coefficient. Numerical results show that mutual information is a more effective approach than the correlation coefficient to measure the stock relationship in a stock market that may undergo large fluctuations of stock prices.
| S-EPMC5905993 | biostudies-literature
Project description:MotivationRecurrent neural networks (RNN) are powerful frameworks to model medical time series records. Recent studies showed improved accuracy of predicting future medical events (e.g., readmission, mortality) by leveraging large amount of high-dimensional data. However, very few studies have explored the ability of RNN in predicting long-term trajectories of recurrent events, which is more informative than predicting one single event in directing medical intervention.MethodsIn this study, we focus on heart failure (HF) which is the leading cause of death among cardiovascular diseases. We present a novel RNN framework named Deep Heart-failure Trajectory Model (DHTM) for modelling the long-term trajectories of recurrent HF. DHTM auto-regressively predicts the future HF onsets of each patient and uses the predicted HF as input to predict the HF event at the next time point. Furthermore, we propose an augmented DHTM named DHTM+C (where "C" stands for co-morbidities), which jointly predicts both the HF and a set of acute co-morbidities diagnoses. To efficiently train the DHTM+C model, we devised a novel RNN architecture to model disease progression implicated in the co-morbidities.ResultsOur deep learning models confers higher prediction accuracy for both the next-step HF prediction and the HF trajectory prediction compared to the baseline non-neural network models and the baseline RNN model. Compared to DHTM, DHTM+C is able to output higher probability of HF for high-risk patients, even in cases where it is only given less than 2 years of data to predict over 5 years of trajectory. We illustrated multiple non-trivial real patient examples of complex HF trajectories, indicating a promising path for creating highly accurate and scalable longitudinal deep learning models for modeling the chronic disease.
| S-EPMC7787457 | biostudies-literature
Project description:Complex network is a powerful tool to discover important information from various types of big data. Although substantial studies have been conducted for the development of stock relation networks, correlation coefficient is dominantly used to measure the relationship between stock pairs. Information theory is much less discussed for this important topic, though mutual information is able to measure nonlinear pairwise relationship. In this work we propose to use part mutual information for developing stock networks. The path-consistency algorithm is used to filter out redundant relationships. Using the Australian stock market data, we develop four stock relation networks using different orders of part mutual information. Compared with the widely used planar maximally filtered graph (PMFG), we can generate networks with cliques of large size. In addition, the large cliques show consistency with the structure of industrial sectors. We also analyze the connectivity and degree distributions of the generated networks. Analysis results suggest that the proposed method is an effective approach to develop stock relation networks using information theory.
| S-EPMC7517323 | biostudies-literature
Project description:BackgroundInference of gene regulatory networks is a key goal in the quest for understanding fundamental cellular processes and revealing underlying relations among genes. With the availability of gene expression data, computational methods aiming at regulatory networks reconstruction are facing challenges posed by the data's high dimensionality, temporal dynamics or measurement noise. We propose an approach based on a novel multi-layer evolutionary trained neuro-fuzzy recurrent network (ENFRN) that is able to select potential regulators of target genes and describe their regulation type.ResultsThe recurrent, self-organizing structure and evolutionary training of our network yield an optimized pool of regulatory relations, while its fuzzy nature avoids noise-related problems. Furthermore, we are able to assign scores for each regulation, highlighting the confidence in the retrieved relations. The approach was tested by applying it to several benchmark datasets of yeast, managing to acquire biologically validated relations among genes.ConclusionsThe results demonstrate the effectiveness of the ENFRN in retrieving biologically valid regulatory relations and providing meaningful insights for better understanding the dynamics of gene regulatory networks. The algorithms and methods described in this paper have been implemented in a Matlab toolbox and are available from: http://bioserver-1.bioacademy.gr/DataRepository/Project_ENFRN_GRN/.
| S-EPMC2848237 | biostudies-literature
Project description:Although individual tumors show surprisingly diverse genomic alterations, these events tend to occur in a limited number of pathways, and alterations that affect the same pathway tend to not co-occur in the same patient. While pathway analysis has been a powerful tool in cancer genomics, our knowledge of oncogenic pathway modules is incomplete. To systematically identify such modules, we have developed a novel method, Mutual Exclusivity Modules in Cancer (MEMo). The method searches and identifies modules characterized by three properties: (1) member genes are recurrently altered across a set of tumor samples; (2) member genes are known to or are likely to participate in the same biological process; and (3) alteration events within the modules are mutually exclusive. MEMo integrates multiple data types and maps genomic alterations to biological pathways. MEMo's mutual exclusivity uses a statistical model that preserves the number of alterations per gene and per sample. The MEMo software, source code and sample data sets are available for download at: http://cbio.mskcc.org/memo.
| S-EPMC5563973 | biostudies-other
Project description:Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state.
| S-EPMC5464651 | biostudies-literature
Project description:BackgroundProbability based statistical learning methods such as mutual information and Bayesian networks have emerged as a major category of tools for reverse engineering mechanistic relationships from quantitative biological data. In this work we introduce a new statistical learning strategy, MI3 that addresses three common issues in previous methods simultaneously: (1) handling of continuous variables, (2) detection of more complex three-way relationships and (3) better differentiation of causal versus confounding relationships. With these improvements, we provide a more realistic representation of the underlying biological system.ResultsWe test the MI3 algorithm using both synthetic and experimental data. In the synthetic data experiment, MI3 achieved an absolute sensitivity/precision of 0.77/0.83 and a relative sensitivity/precision both of 0.99. In addition, MI3 significantly outperformed the control methods, including Bayesian networks, classical two-way mutual information and a discrete version of MI3. We then used MI3 and control methods to infer a regulatory network centered at the MYC transcription factor from a published microarray dataset. Models selected by MI3 were numerically and biologically distinct from those selected by control methods. Unlike control methods, MI3 effectively differentiated true causal models from confounding models. MI3 recovered major MYC cofactors, and revealed major mechanisms involved in MYC dependent transcriptional regulation, which are strongly supported by literature. The MI3 network showed that limited sets of regulatory mechanisms are employed repeatedly to control the expression of large number of genes.ConclusionOverall, our work demonstrates that MI3 outperforms the frequently used control methods, and provides a powerful method for inferring mechanistic relationships underlying biological and other complex systems. The MI3 method is implemented in R in the "mi3" package, available under the GNU GPL from http://sysbio.engin.umich.edu/~luow/downloads.php and from the R package archive CRAN.
| S-EPMC2613931 | biostudies-literature
Project description:High-throughput technologies have led to the generation of an increasing amount of data in different areas of biology. Datasets capturing the cell's response to its intra- and extra-cellular microenvironment allows such data to be incorporated as signed and directed graphs or influence networks. These prior knowledge networks (PKNs) represent our current knowledge of the causality of cellular signal transduction. New signalling data is often examined and interpreted in conjunction with PKNs. However, different biological contexts, such as cell type or disease states, may have distinct variants of signalling pathways, resulting in the misinterpretation of new data. The identification of inconsistencies between measured data and signalling topologies, as well as the training of PKNs using context specific datasets (PKN contextualization), are necessary conditions to construct reliable, predictive models, which are current challenges in the systems biology of cell signalling. Here we present PRUNET, a user-friendly software tool designed to address the contextualization of a PKNs to specific experimental conditions. As the input, the algorithm takes a PKN and the expression profile of two given stable steady states or cellular phenotypes. The PKN is iteratively pruned using an evolutionary algorithm to perform an optimization process. This optimization rests in a match between predicted attractors in a discrete logic model (Boolean) and a Booleanized representation of the phenotypes, within a population of alternative subnetworks that evolves iteratively. We validated the algorithm applying PRUNET to four biological examples and using the resulting contextualized networks to predict missing expression values and to simulate well-characterized perturbations. PRUNET constitutes a tool for the automatic curation of a PKN to make it suitable for describing biological processes under particular experimental conditions. The general applicability of the implemented algorithm makes PRUNET suitable for a variety of biological processes, for instance cellular reprogramming or transitions between healthy and disease states.
| S-EPMC4461287 | biostudies-literature
Project description:Regional innovation performance is an important indicator for decision-making regarding the implementation of policies intended to support innovation. However, patterns in regional innovation structures are becoming increasingly diverse, complex and nonlinear. To address these issues, this study aims to develop a model based on a multi-output neural network. Both intra- and inter-regional determinants of innovation performance are empirically investigated using data from the 4th and 5th Community Innovation Surveys of NUTS 2 (Nomenclature of Territorial Units for Statistics) regions. The results suggest that specific innovation strategies must be developed based on the current state of input attributes in the region. Thus, it is possible to develop appropriate strategies and targeted interventions to improve regional innovation performance. We demonstrate that support of entrepreneurship is an effective instrument of innovation policy. We also provide empirical support that both business and government R&D activity have a sigmoidal effect, implying that the most effective R&D support should be directed to regions with below-average and average R&D activity. We further show that the multi-output neural network outperforms traditional statistical and machine learning regression models. In general, therefore, it seems that the proposed model can effectively reflect both the multiple-output nature of innovation performance and the interdependency of the output attributes.
| S-EPMC5624612 | biostudies-literature
Project description:BACKGROUND: Cancer is a complex disease commonly characterized by the disrupted activity of several cancer-related genes such as oncogenes and tumor-suppressor genes. Previous studies suggest that the process of tumor progression to malignancy is dynamic and can be traced by changes in gene expression. Despite the enormous efforts made for differential expression detection and biomarker discovery, few methods have been designed to model the gene expression level to tumor stage during malignancy progression. Such models could help us understand the dynamics and simplify or reveal the complexity of tumor progression. METHODS: We have modeled an on-off state of gene activation per sample then per stage to select gene expression profiles associated to tumor progression. The selection is guided by statistical significance of profiles based on random permutated datasets. RESULTS: We show that our method identifies expected profiles corresponding to oncogenes and tumor suppressor genes in a prostate tumor progression dataset. Comparisons with other methods support our findings and indicate that a considerable proportion of significant profiles is not found by other statistical tests commonly used to detect differential expression between tumor stages nor found by other tailored methods. Ontology and pathway analysis concurred with these findings. CONCLUSIONS: Results suggest that our methodology may be a valuable tool to study tumor malignancy progression, which might reveal novel cancer therapies.
| S-EPMC3691825 | biostudies-other