Detection of Epigenomic Network Community Oncomarkers

In this paper we propose network methodology to infer prognostic cancer biomarkers based on the epigenetic pattern DNA methylation. Epigenetic processes such as DNA methylation reflect environmental risk factors, and are increasingly recognised for their fundamental role in diseases such as cancer. DNA methylation is a gene-regulatory pattern, and hence provides a means by which to assess genomic regulatory interactions. Network models are a natural way to represent and analyse groups of such interactions. The utility of network models also increases as the quantity of data and number of variables increase, making them increasingly relevant to large-scale genomic studies. We propose methodology to infer prognostic genomic networks from a DNA methylation-based measure of genomic interaction and association. We then show how to identify prognostic biomarkers from such networks, which we term `network community oncomarkers'. We illustrate the power of our proposed methodology in the context of a large publicly available breast cancer dataset

Unified functional network and nonlinear time series analysis for complex systems science: The pyunicorn package

We introduce the \texttt{pyunicorn} (Pythonic unified complex network and recurrence analysis toolbox) open source software package for applying and combining modern methods of data analysis and modeling from complex network theory and nonlinear time series analysis. \texttt{pyunicorn} is a fully object-oriented and easily parallelizable package written in the language Python. It allows for the construction of functional networks such as climate networks in climatology or functional brain networks in neuroscience representing the structure of statistical interrelationships in large data sets of time series and, subsequently, investigating this structure using advanced methods of complex network theory such as measures and models for spatial networks, networks of interacting networks, node-weighted statistics or network surrogates. Additionally, \texttt{pyunicorn} provides insights into the nonlinear dynamics of complex systems as recorded in uni- and multivariate time series from a non-traditional perspective by means of recurrence quantification analysis (RQA), recurrence networks, visibility graphs and construction of surrogate time series. The range of possible applications of the library is outlined, drawing on several examples mainly from the field of climatology.Comment: 28 pages, 17 figure

Age-related relationships among peripheral B lymphocyte subpopulations

An immunological data-driven model is proposed, for age related changes in the network of relationships among cell quantities of eight peripheral B lymphocyte subpopulations, that is, cells exhibiting all combinations of three specific receptor clusters (CD27, CD23, CD5). The model is based on immunological data (quantities of cells exhibiting CD19, characterizing B lymphocytes) from about six thousands patients, having an age ranging between one day and ninety-five years, by means of a suitably combination of data analysis methods, such as piecewise linear regression models. With relaxed values for statistically significant models (coefficient p-values bounded by 0.05), we found a network holding for all ages, that likely represents the general assessment of adaptive immune system for healthy human beings. When statistical validation comes to be more restrictive, we found that some of these interactions are lost with aging, as widely observed in medical literature. Namely, interesting (inverse or directed) proportions are highlighted among mutual quantities of a partition of peripheral B lymphocytes

A temporal precedence based clustering method for gene expression microarray data

Background: Time-course microarray experiments can produce useful data which can help in understanding the underlying dynamics of the system. Clustering is an important stage in microarray data analysis where the data is grouped together according to certain characteristics. The majority of clustering techniques are based on distance or visual similarity measures which may not be suitable for clustering of temporal microarray data where the sequential nature of time is important. We present a Granger causality based technique to cluster temporal microarray gene expression data, which measures the interdependence between two time-series by statistically testing if one time-series can be used for forecasting the other time-series or not. Results: A gene-association matrix is constructed by testing temporal relationships between pairs of genes using the Granger causality test. The association matrix is further analyzed using a graph-theoretic technique to detect highly connected components representing interesting biological modules. We test our approach on synthesized datasets and real biological datasets obtained for Arabidopsis thaliana. We show the effectiveness of our approach by analyzing the results using the existing biological literature. We also report interesting structural properties of the association network commonly desired in any biological system. Conclusions: Our experiments on synthesized and real microarray datasets show that our approach produces encouraging results. The method is simple in implementation and is statistically traceable at each step. The method can produce sets of functionally related genes which can be further used for reverse-engineering of gene circuits

Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.

MotivationMultiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.ResultsWe performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementationDatasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary informationSupplementary data are available at Bioinformatics online

Statistical Mechanics and Information-Theoretic Perspectives on Complexity in the Earth System

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