Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Simplifying functional network representation and interpretation through causality clustering.

ABSTRACT: Functional networks, i.e. networks representing the interactions between the elements of a complex system and reconstructed from the observed elements' dynamics, are becoming a fundamental tool to unravel the structures created by the movement of information in systems like the human brain. They also present drawbacks, one of the most important being the inherent difficulty in representing and interpreting the resulting structures for large number of nodes and links. I here propose a causality clustering approach, based on grouping nodes into clusters according to their similarity in the overall information dynamics, the latter one being measured by a causality metric. The whole system can then arbitrarily be simplified, with nodes being grouped in e.g. sources, brokers and sinks of information. The advantages and limitations of the proposed approach are discussed using a set of synthetic and real-world data sets, the latter ones representing two neuroscience and technological problems.

SUBMITTER: Zanin M

PROVIDER: S-EPMC8319423 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Simplifying functional network representation and interpretation through causality clustering.

Zanin Massimiliano M

Scientific reports 20210728 1

Functional networks, i.e. networks representing the interactions between the elements of a complex system and reconstructed from the observed elements' dynamics, are becoming a fundamental tool to unravel the structures created by the movement of information in systems like the human brain. They also present drawbacks, one of the most important being the inherent difficulty in representing and interpreting the resulting structures for large number of nodes and links. I here propose a causality c ...[more]

PMID: 34321541

Similar Datasets

Optimizing functional network representation of multivariate time series.

Project description:By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks.

| S-EPMC3433690 | biostudies-other

Clustering Schizophrenia Genes by Their Temporal Expression Patterns Aids Functional Interpretation.

Project description:BackgroundSchizophrenia is a highly heritable brain disorder with a typical symptom onset in early adulthood. The 2-hit hypothesis posits that schizophrenia results from differential early neurodevelopment, predisposing an individual, followed by a disruption of later brain maturational processes that trigger the onset of symptoms.Study designWe applied hierarchical clustering to transcription levels of 345 genes previously linked to schizophrenia, derived from cortical tissue samples from 56 donors across the lifespan. We subsequently calculated clustered-specific polygenic risk scores for 743 individuals with schizophrenia and 743 sex- and age-matched healthy controls.Study resultsClustering revealed a set of 183 genes that was significantly upregulated prenatally and downregulated postnatally and 162 genes that showed the opposite pattern. The prenatally upregulated set of genes was functionally annotated to fundamental cell cycle processes, while the postnatally upregulated set was associated with the immune system and neuronal communication. We found an interaction between the 2 scores; higher prenatal polygenic risk showed a stronger association with schizophrenia diagnosis at higher levels of postnatal polygenic risk. Importantly, this finding was replicated in an independent clinical cohort of 3233 individuals.ConclusionsWe provide genetics-based evidence that schizophrenia is shaped by disruptions of separable biological processes acting at distinct phases of neurodevelopment. The modeling of genetic risk factors that moderate each other's effect, informed by the timing of their expression, will aid in a better understanding of the development of schizophrenia.

| S-EPMC10919784 | biostudies-literature

Causality in cancer research: a journey through models in molecular epidemiology and their philosophical interpretation.

Project description:In the last decades, Systems Biology (including cancer research) has been driven by technology, statistical modelling and bioinformatics. In this paper we try to bring biological and philosophical thinking back. We thus aim at making different traditions of thought compatible: (a) causality in epidemiology and in philosophical theorizing-notably, the "sufficient-component-cause framework" and the "mark transmission" approach; (b) new acquisitions about disease pathogenesis, e.g. the "branched model" in cancer, and the role of biomarkers in this process; (c) the burgeoning of omics research, with a large number of "signals" and of associations that need to be interpreted. In the paper we summarize first the current views on carcinogenesis, and then explore the relevance of current philosophical interpretations of "cancer causes". We try to offer a unifying framework to incorporate biomarkers and omic data into causal models, referring to a position called "evidential pluralism". According to this view, causal reasoning is based on both "evidence of difference-making" (e.g. associations) and on "evidence of underlying biological mechanisms". We conceptualize the way scientists detect and trace signals in terms of information transmission, which is a generalization of the mark transmission theory developed by philosopher Wesley Salmon. Our approach is capable of helping us conceptualize how heterogeneous factors such as micro and macro-biological and psycho-social-are causally linked. This is important not only to understand cancer etiology, but also to design public health policies that target the right causal factors at the macro-level.

| S-EPMC5463386 | biostudies-literature

Extracting neuronal functional network dynamics via adaptive Granger causality analysis.

Project description:Quantifying the functional relations between the nodes in a network based on local observations is a key challenge in studying complex systems. Most existing time series analysis techniques for this purpose provide static estimates of the network properties, pertain to stationary Gaussian data, or do not take into account the ubiquitous sparsity in the underlying functional networks. When applied to spike recordings from neuronal ensembles undergoing rapid task-dependent dynamics, they thus hinder a precise statistical characterization of the dynamic neuronal functional networks underlying adaptive behavior. We develop a dynamic estimation and inference paradigm for extracting functional neuronal network dynamics in the sense of Granger, by integrating techniques from adaptive filtering, compressed sensing, point process theory, and high-dimensional statistics. We demonstrate the utility of our proposed paradigm through theoretical analysis, algorithm development, and application to synthetic and real data. Application of our techniques to two-photon Ca2+ imaging experiments from the mouse auditory cortex reveals unique features of the functional neuronal network structures underlying spontaneous activity at unprecedented spatiotemporal resolution. Our analysis of simultaneous recordings from the ferret auditory and prefrontal cortical areas suggests evidence for the role of rapid top-down and bottom-up functional dynamics across these areas involved in robust attentive behavior.

| S-EPMC5924897 | biostudies-literature

Functional connectivity of default mode network components: correlation, anticorrelation, and causality.

Project description:The default mode network (DMN), based in ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), exhibits higher metabolic activity at rest than during performance of externally oriented cognitive tasks. Recent studies have suggested that competitive relationships between the DMN and various task-positive networks involved in task performance are intrinsically represented in the brain in the form of strong negative correlations (anticorrelations) between spontaneous fluctuations in these networks. Most neuroimaging studies characterize the DMN as a homogenous network, thus few have examined the differential contributions of DMN components to such competitive relationships. Here, we examined functional differentiation within the DMN, with an emphasis on understanding competitive relationships between this and other networks. We used a seed correlation approach on resting-state data to assess differences in functional connectivity between these two regions and their anticorrelated networks. While the positively correlated networks for the vmPFC and PCC seeds largely overlapped, the anticorrelated networks for each showed striking differences. Activity in vmPFC negatively predicted activity in parietal visual spatial and temporal attention networks, whereas activity in PCC negatively predicted activity in prefrontal-based motor control circuits. Granger causality analyses suggest that vmPFC and PCC exert greater influence on their anticorrelated networks than the other way around, suggesting that these two default mode nodes may directly modulate activity in task-positive networks. Thus, the two major nodes comprising the DMN are differentiated with respect to the specific brain systems with which they interact, suggesting greater heterogeneity within this network than is commonly appreciated.

| S-EPMC3654104 | biostudies-literature

Computational drug repositioning through heterogeneous network clustering.

Project description:Given the costly and time consuming process and high attrition rates in drug discovery and development, drug repositioning or drug repurposing is considered as a viable strategy both to replenish the drying out drug pipelines and to surmount the innovation gap. Although there is a growing recognition that mechanistic relationships from molecular to systems level should be integrated into drug discovery paradigms, relatively few studies have integrated information about heterogeneous networks into computational drug-repositioning candidate discovery platforms.Using known disease-gene and drug-target relationships from the KEGG database, we built a weighted disease and drug heterogeneous network. The nodes represent drugs or diseases while the edges represent shared gene, biological process, pathway, phenotype or a combination of these features. We clustered this weighted network to identify modules and then assembled all possible drug-disease pairs (putative drug repositioning candidates) from these modules. We validated our predictions by testing their robustness and evaluated them by their overlap with drug indications that were either reported in published literature or investigated in clinical trials.Previous computational approaches for drug repositioning focused either on drug-drug and disease-disease similarity approaches whereas we have taken a more holistic approach by considering drug-disease relationships also. Further, we considered not only gene but also other features to build the disease drug networks. Despite the relative simplicity of our approach, based on the robustness analyses and the overlap of some of our predictions with drug indications that are under investigation, we believe our approach could complement the current computational approaches for drug repositioning candidate discovery.

| S-EPMC4029299 | biostudies-literature

Spatially weighted functional clustering of river network data.

Project description:Incorporating spatial covariance into clustering has previously been considered for functional data to identify groups of functions which are similar across space. However, in the majority of situations that have been considered until now the most appropriate metric has been Euclidean distance. Directed networks present additional challenges in terms of estimating spatial covariance due to their complex structure. Although suitable river network covariance models have been proposed for use with stream distance, where distance is computed along the stream network, these models have not been extended for contexts where the data are functional, as is often the case with environmental data. The paper develops a method of calculating spatial covariance between functions from sites along a river network and applies the measure as a weight within functional hierarchical clustering. Levels of nitrate pollution on the River Tweed in Scotland are considered with the aim of identifying groups of monitoring stations which display similar spatiotemporal characteristics.

| S-EPMC4407953 | biostudies-literature

Unsupervised Clustering of Missense Variants in HNF1A Using Multidimensional Functional Data Aids Clinical Interpretation.

Project description:Exome sequencing in diabetes presents a diagnostic challenge because depending on frequency, functional impact, and genomic and environmental contexts, HNF1A variants can cause maturity-onset diabetes of the young (MODY), increase type 2 diabetes risk, or be benign. A correct diagnosis matters as it informs on treatment, progression, and family risk. We describe a multi-dimensional functional dataset of 73 HNF1A missense variants identified in exomes of 12,940 individuals. Our aim was to develop an analytical framework for stratifying variants along the HNF1A phenotypic continuum to facilitate diagnostic interpretation. HNF1A variant function was determined by four different molecular assays. Structure of the multi-dimensional dataset was explored using principal component analysis, k-means, and hierarchical clustering. Weights for tissue-specific isoform expression and functional domain were integrated. Functionally annotated variant subgroups were used to re-evaluate genetic diagnoses in national MODY diagnostic registries. HNF1A variants demonstrated a range of behaviors across the assays. The structure of the multi-parametric data was shaped primarily by transactivation. Using unsupervised learning methods, we obtained high-resolution functional clusters of the variants that separated known causal MODY variants from benign and type 2 diabetes risk variants and led to reclassification of 4% and 9% of HNF1A variants identified in the UK and Norway MODY diagnostic registries, respectively. Our proof-of-principle analyses facilitated informative stratification of HNF1A variants along the continuum, allowing improved evaluation of clinical significance, management, and precision medicine in diabetes clinics. Transcriptional activity appears a superior readout supporting pursuit of transactivation-centric experimental designs for high-throughput functional screens.

| S-EPMC7536579 | biostudies-literature

From the Cover: Simplifying the representation of complex free-energy landscapes using sketch-map.

Project description:A new scheme, sketch-map, for obtaining a low-dimensional representation of the region of phase space explored during an enhanced dynamics simulation is proposed. We show evidence, from an examination of the distribution of pairwise distances between frames, that some features of the free-energy surface are inherently high-dimensional. This makes dimensionality reduction problematic because the data does not satisfy the assumptions made in conventional manifold learning algorithms We therefore propose that when dimensionality reduction is performed on trajectory data one should think of the resultant embedding as a quickly sketched set of directions rather than a road map. In other words, the embedding tells one about the connectivity between states but does not provide the vectors that correspond to the slow degrees of freedom. This realization informs the development of sketch-map, which endeavors to reproduce the proximity information from the high-dimensionality description in a space of lower dimensionality even when a faithful embedding is not possible.

| S-EPMC3156203 | biostudies-literature

HetFCM: functional co-module discovery by heterogeneous network co-clustering.

Project description:Functional molecular module (i.e., gene-miRNA co-modules and gene-miRNA-lncRNA triple-layer modules) analysis can dissect complex regulations underlying etiology or phenotypes. However, current module detection methods lack an appropriate usage and effective model of multi-omics data and cross-layer regulations of heterogeneous molecules, causing the loss of critical genetic information and corrupting the detection performance. In this study, we propose a heterogeneous network co-clustering framework (HetFCM) to detect functional co-modules. HetFCM introduces an attributed heterogeneous network to jointly model interplays and multi-type attributes of different molecules, and applies multiple variational graph autoencoders on the network to generate cross-layer association matrices, then it performs adaptive weighted co-clustering on association matrices and attribute data to identify co-modules of heterogeneous molecules. Empirical study on Human and Maize datasets reveals that HetFCM can find out co-modules characterized with denser topology and more significant functions, which are associated with human breast cancer (subtypes) and maize phenotypes (i.e., lipid storage, drought tolerance and oil content). HetFCM is a useful tool to detect co-modules and can be applied to multi-layer functional modules, yielding novel insights for analyzing molecular mechanisms. We also developed a user-friendly module detection and analysis tool and shared it at http://www.sdu-idea.cn/FMDTool.

| S-EPMC10853805 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data