Dataset Information

Reconstructing missing complex networks against adversarial interventions.

ABSTRACT: Interactions within complex network components define their operational modes, collective behaviors and global functionality. Understanding the role of these interactions is limited by either sensing methodologies or intentional adversarial efforts that sabotage the network structure. To overcome the partial observability and infer with good fidelity the unobserved network structures (latent subnetworks that are not random samples of the full network), we propose a general causal inference framework for reconstructing network structures under unknown adversarial interventions. We explore its applicability in both biological and social systems to recover the latent structures of human protein complex interactions and brain connectomes, as well as to infer the camouflaged social network structure in a simulated removal process. The demonstrated effectiveness establishes its good potential for capturing hidden information in much broader research domains.

SUBMITTER: Xue Y

PROVIDER: S-EPMC6465316 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Reconstructing missing complex networks against adversarial interventions.

Xue Yuankun Y Bogdan Paul P

Nature communications 20190415 1

Interactions within complex network components define their operational modes, collective behaviors and global functionality. Understanding the role of these interactions is limited by either sensing methodologies or intentional adversarial efforts that sabotage the network structure. To overcome the partial observability and infer with good fidelity the unobserved network structures (latent subnetworks that are not random samples of the full network), we propose a general causal inference frame ...[more]

PMID: 30988308

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Project description:BackgroundMissing data is a pervasive problem in clinical research. Generative adversarial imputation nets (GAIN), a novel machine learning data imputation approach, has the potential to substitute missing data accurately and efficiently but has not yet been evaluated in empirical big clinical datasets.ObjectivesThis study aimed to evaluate the accuracy of GAIN in imputing missing values in large real-world clinical datasets with mixed-type variables. The computation efficiency of GAIN was also evaluated. The performance of GAIN was compared with other commonly used methods, MICE and missForest.MethodsTwo real world clinical datasets were used. The first was that of a cohort study on the long-term outcomes of patients with diabetes (50,000 complete cases), and the second was of a cohort study on the effectiveness of a risk assessment and management programme for patients with hypertension (10,000 complete cases). Missing data (missing at random) to independent variables were simulated at different missingness rates (20, 50%). The normalized root mean square error (NRMSE) between imputed values and real values for continuous variables and the proportion of falsely classified (PFC) for categorical variables were used to measure imputation accuracy. Computation time per imputation for each method was recorded. The differences in accuracy of different imputation methods were compared using ANOVA or non-parametric test.ResultsBoth missForest and GAIN were more accurate than MICE. GAIN showed similar accuracy as missForest when the simulated missingness rate was 20%, but was more accurate when the simulated missingness rate was 50%. GAIN was the most accurate for the imputation of skewed continuous and imbalanced categorical variables at both missingness rates. GAIN had a much higher computation speed (32 min on PC) comparing to that of missForest (1300 min) when the sample size is 50,000.ConclusionGAIN showed better accuracy as an imputation method for missing data in large real-world clinical datasets compared to MICE and missForest, and was more resistant to high missingness rate (50%). The high computation speed is an added advantage of GAIN in big clinical data research. It holds potential as an accurate and efficient method for missing data imputation in future big data clinical research.Trial registrationClinicalTrials.gov ID: NCT03299010 ; Unique Protocol ID: HKUCTR-2232.

Project description:BackgroundHi-C data have been widely used to reconstruct chromosomal three-dimensional (3D) structures. One of the key limitations of Hi-C is the unclear relationship between spatial distance and the number of Hi-C contacts. Many methods used a fixed parameter when converting the number of Hi-C contacts to wish distances. However, a single parameter cannot properly explain the relationship between wish distances and genomic distances or the locations of topologically associating domains (TADs).ResultsWe have addressed one of the key issues of using Hi-C data, that is, the unclear relationship between spatial distances and the number of Hi-C contacts, which is crucial to understand significant biological functions, such as the enhancer-promoter interactions. Specifically, we developed a new method to infer this converting parameter and pairwise Euclidean distances based on the topology of the Hi-C complex network (HiCNet). The inferred distances were modeled by clustering coefficient and multiple other types of constraints. We found that our inferred distances between bead-pairs within the same TAD were apparently smaller than those distances between bead-pairs from different TADs. Our inferred distances had a higher correlation with fluorescence in situ hybridization (FISH) data, fitted the localization patterns of Xist transcripts on DNA, and better matched 156 pairs of protein-enabled long-range chromatin interactions detected by ChIA-PET. Using the inferred distances and another round of optimization, we further reconstructed 40?kb high-resolution 3D chromosomal structures of mouse male ES cells. The high-resolution structures successfully illustrate TADs and DNA loops (peaks in Hi-C contact heatmaps) that usually indicate enhancer-promoter interactions.ConclusionsWe developed a novel method to infer the wish distances between DNA bead-pairs from Hi-C contacts. High-resolution 3D structures of chromosomes were built based on the newly-inferred wish distances. This whole process has been implemented as a tool named HiCNet, which is publicly available at http://dna.cs.miami.edu/HiCNet/ .

Dataset Information

Reconstructing missing complex networks against adversarial interventions.

Publications

Reconstructing missing complex networks against adversarial interventions.

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