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Detecting the ultra low dimensionality of real networks.

ABSTRACT: Reducing dimension redundancy to find simplifying patterns in high-dimensional datasets and complex networks has become a major endeavor in many scientific fields. However, detecting the dimensionality of their latent space is challenging but necessary to generate efficient embeddings to be used in a multitude of downstream tasks. Here, we propose a method to infer the dimensionality of networks without the need for any a priori spatial embedding. Due to the ability of hyperbolic geometry to capture the complex connectivity of real networks, we detect ultra low dimensionality far below values reported using other approaches. We applied our method to real networks from different domains and found unexpected regularities, including: tissue-specific biomolecular networks being extremely low dimensional; brain connectomes being close to the three dimensions of their anatomical embedding; and social networks and the Internet requiring slightly higher dimensionality. Beyond paving the way towards an ultra efficient dimensional reduction, our findings help address fundamental issues that hinge on dimensionality, such as universality in critical behavior.

SUBMITTER: Almagro P

PROVIDER: S-EPMC9569339 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Detecting the ultra low dimensionality of real networks.

Almagro Pedro P Boguñá Marián M Serrano M Ángeles MÁ

Nature communications 20221015 1

Reducing dimension redundancy to find simplifying patterns in high-dimensional datasets and complex networks has become a major endeavor in many scientific fields. However, detecting the dimensionality of their latent space is challenging but necessary to generate efficient embeddings to be used in a multitude of downstream tasks. Here, we propose a method to infer the dimensionality of networks without the need for any a priori spatial embedding. Due to the ability of hyperbolic geometry to cap ...[more]

PMID: 36243754

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Project description:BackgroundSystems wide modeling and analysis of signaling networks is essential for understanding complex cellular behaviors, such as the biphasic responses to different combinations of cytokines and growth factors. For example, tumor necrosis factor (TNF) can act as a proapoptotic or prosurvival factor depending on its concentration, the current state of signaling network and the presence of other cytokines. To understand combinatorial regulation in such systems, new computational approaches are required that can take into account non-linear interactions in signaling networks and provide tools for clustering, visualization and predictive modeling.ResultsHere we extended and applied an unsupervised non-linear dimensionality reduction approach, Isomap, to find clusters of similar treatment conditions in two cell signaling networks: (I) apoptosis signaling network in human epithelial cancer cells treated with different combinations of TNF, epidermal growth factor (EGF) and insulin and (II) combination of signal transduction pathways stimulated by 21 different ligands based on AfCS double ligand screen data. For the analysis of the apoptosis signaling network we used the Cytokine compendium dataset where activity and concentration of 19 intracellular signaling molecules were measured to characterise apoptotic response to TNF, EGF and insulin. By projecting the original 19-dimensional space of intracellular signals into a low-dimensional space, Isomap was able to reconstruct clusters corresponding to different cytokine treatments that were identified with graph-based clustering. In comparison, Principal Component Analysis (PCA) and Partial Least Squares - Discriminant analysis (PLS-DA) were unable to find biologically meaningful clusters. We also showed that by using Isomap components for supervised classification with k-nearest neighbor (k-NN) and quadratic discriminant analysis (QDA), apoptosis intensity can be predicted for different combinations of TNF, EGF and insulin. Prediction accuracy was highest when early activation time points in the apoptosis signaling network were used to predict apoptosis rates at later time points. Extended Isomap also outperformed PCA on the AfCS double ligand screen data. Isomap identified more functionally coherent clusters than PCA and captured more information in the first two-components. The Isomap projection performs slightly worse when more signaling networks are analyzed; suggesting that the mapping function between cues and responses becomes increasingly non-linear when large signaling pathways are considered.ConclusionWe developed and applied extended Isomap approach for the analysis of cell signaling networks. Potential biological applications of this method include characterization, visualization and clustering of different treatment conditions (i.e. low and high doses of TNF) in terms of changes in intracellular signaling they induce.

Project description:BackgroundDetection of gene-gene interaction (GGI) is a key challenge towards solving the problem of missing heritability in genetics. The multifactor dimensionality reduction (MDR) method has been widely studied for detecting GGIs. MDR reduces the dimensionality of multi-factor by means of binary classification into high-risk (H) or low-risk (L) groups. Unfortunately, this simple binary classification does not reflect the uncertainty of H/L classification. Thus, we proposed Fuzzy MDR to overcome limitations of binary classification by introducing the degree of membership of two fuzzy sets H/L. While Fuzzy MDR demonstrated higher power than that of MDR, its performance is highly dependent on the several tuning parameters. In real applications, it is not easy to choose appropriate tuning parameter values.ResultIn this work, we propose an empirical fuzzy MDR (EF-MDR) which does not require specifying tuning parameters values. Here, we propose an empirical approach to estimating the membership degree that can be directly estimated from the data. In EF-MDR, the membership degree is estimated by the maximum likelihood estimator of the proportion of cases(controls) in each genotype combination. We also show that the balanced accuracy measure derived from this new membership function is a linear function of the standard chi-square statistics. This relationship allows us to perform the standard significance test using p-values in the MDR framework without permutation. Through two simulation studies, the power of the proposed EF-MDR is shown to be higher than those of MDR and Fuzzy MDR. We illustrate the proposed EF-MDR by analyzing Crohn's disease (CD) and bipolar disorder (BD) in the Wellcome Trust Case Control Consortium (WTCCC) dataset.ConclusionWe propose an empirical Fuzzy MDR for detecting GGI using the maximum likelihood of the proportion of cases(controls) as the membership degree of the genotype combination. The program written in R for EF-MDR is available at http://statgen.snu.ac.kr/software/EF-MDR .

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Detecting the ultra low dimensionality of real networks.

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Detecting the ultra low dimensionality of real networks.

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