Static Protein-protein Interaction Networks Research Articles

A Construction Method of Dynamic Protein Interaction Networks by Using Relevant Features of Gene Expression Data.

Essential proteins play an important role in various life activities and are considered to be a vital part of the organism. Gene expression data are an important dataset to construct dynamic protein-protein interaction networks (DPIN). The existing methods for the construction of DPINs generally utilize all features (or the features in a cycle) of the gene expression data. However, the features observed from successive time points tend to be highly correlated, and thus there are some redundant and irrelevant features in the gene expression data, which will influence the quality of the constructed network and the predictive performance of essential proteins. To address this problem, we propose a construction method of DPINs by using selected relevant features rather than continuous and periodic features. We adopt an improved unsupervised feature selection method based on Laplacian algorithm to remove irrelevant and redundant features from gene expression data, then integrate the chosen relevant features into the static protein-protein interaction network (SPIN) to construct a more concise and effective DPIN (FS-DPIN). To evaluate the effectiveness of the FS-DPIN, we apply 15 network-based centrality methods on the FS-DPIN and compare the results with those on the SPIN and the existing DPINs. Then the predictive performance of the 15 centrality methods is validated in terms of sensitivity, specificity, positive predictive value, negative predictive value, F-measure, accuracy, Jackknife and AUPRC. The experimental results show that the FS-DPIN is superior to the existing DPINs in the identification accuracy of essential proteins.

Temporal-Spatial Analysis of the Essentiality of Hub Proteins in Protein-Protein Interaction Networks

Hubs are generally defined as nodes with a high degree centrality, and they are important for maintaining the stability of complex networks. Previous studies have shown that hub proteins tend to be essential in protein-protein interaction (PPI) networks, providing us with a new way to analyze the essentiality of proteins. Unfortunately, most of the existing studies leverage static PPI networks that are both incomplete and noisy and ignore the temporal and spatial characteristics of PPI networks. Benefiting from the development of high-throughput technologies, abundant multi-biological datasets have been accumulated and can be used for network analysis. To reexamine the relationship between the network centrality and protein essentiality in PPI networks, in this study, we integrated PPI networks with gene expression data and subcellular localization information to construct temporal-spatial dynamic PPI networks. Based on the constructed temporal-spatial dynamic PPI networks, we introduced the maximum degree centrality (MDC) method to evaluate the essentiality of hub proteins. Our results illustrate that the integration of gene expression data or subcellular localization information can significantly reduce noise effects and improve the identification accuracy of essential proteins through the temporal-spatial analysis with disparate sources of PPI networks. Moreover, we redefined hubs and classified them into two types: temporospatial hubs and static hubs. The results show that temporospatial hub proteins are more likely to be essential.

Relation Extraction of Protein Complexes from Dynamic Protein-Protein Interaction Network.

Background: Dynamic protein-protein interaction networks (DPPIN) can confirm the conditional and temporal features of proteins and protein complexes. In addition, the relation of protein complexes in dynamic networks can provide useful information in understanding the dynamic functionality of PPI networks. Objective: In this paper, an algorithm is presented to discover the temporal association rule from the dynamic PPIN dataset.Material and Methods: In this analytical study, the static protein-protein interaction network is transformed into a dynamic network using the gene expression thresholding to extract the protein complex relations. The number of presented proteins of the dynamic network is large at each time point. This number will increase for extraction of multidimensional rules at different times. By mapping the gold standard protein complexes as reference protein complexes, the number of items decreases from active proteins to protein complexes at each transaction. Extracted sub graphs as protein complexes, at each time point, are weighted according to the reference protein complexes similarity degrees. Mega-transactions and extended items are created based on occurrence bitmap matrix of the reference complexes. Rules will be extracted based on Mega-transactions of protein complexes.Results: The proposed method has been evaluated using gold standard protein complex rules. The amount of extracted rules from Biogrid datasets and protein complexes are 281, with support 0.2.Conclusion: The characteristic of the proposed algorithm is the simultaneous extraction of intra-transaction and inter-transaction rules. The results evaluation using EBI data shows the efficiency of the proposed algorithm.

Relation Extraction of Protein Complexes from Dynamic Protein-Protein Interaction Network

Background: Dynamic protein-protein interaction networks (DPPIN) can confirm the conditional and temporal features of proteins and protein complexes. In addition, the relation of protein complexes in dynamic networks can provide useful information in understanding the dynamic functionality of PPI networks. Objective: In this paper, an algorithm is presented to discover the temporal association rule from the dynamic PPIN dataset.Material and Methods: In this analytical study, the static protein-protein interaction network is transformed into a dynamic network using the gene expression thresholding to extract the protein complex relations. The number of presented proteins of the dynamic network is large at each time point. This number will increase for extraction of multidimensional rules at different times. By mapping the gold standard protein complexes as reference protein complexes, the number of items decreases from active proteins to protein complexes at each transaction. Extracted sub graphs as protein complexes, at each time point, are weighted according to the reference protein complexes similarity degrees. Mega-transactions and extended items are created based on occurrence bitmap matrix of the reference complexes. Rules will be extracted based on Mega-transactions of protein complexes. Results: The proposed method has been evaluated using gold standard protein complex rules. The amount of extracted rules from Biogrid datasets and protein complexes are 281, with support 0.2. Conclusion: The characteristic of the proposed algorithm is the simultaneous extraction of intra-transaction and inter-transaction rules. The results evaluation using EBI data shows the efficiency of the proposed algorithm.

Ensemble disease gene prediction by clinical sample-based networks

BackgroundDisease gene prediction is a critical and challenging task. Many computational methods have been developed to predict disease genes, which can reduce the money and time used in the experimental validation. Since proteins (products of genes) usually work together to achieve a specific function, biomolecular networks, such as the protein-protein interaction (PPI) network and gene co-expression networks, are widely used to predict disease genes by analyzing the relationships between known disease genes and other genes in the networks. However, existing methods commonly use a universal static PPI network, which ignore the fact that PPIs are dynamic, and PPIs in various patients should also be different.ResultsTo address these issues, we develop an ensemble algorithm to predict disease genes from clinical sample-based networks (EdgCSN). The algorithm first constructs single sample-based networks for each case sample of the disease under study. Then, these single sample-based networks are merged to several fused networks based on the clustering results of the samples. After that, logistic models are trained with centrality features extracted from the fused networks, and an ensemble strategy is used to predict the finial probability of each gene being disease-associated. EdgCSN is evaluated on breast cancer (BC), thyroid cancer (TC) and Alzheimer’s disease (AD) and obtains AUC values of 0.970, 0.971 and 0.966, respectively, which are much better than the competing algorithms. Subsequent de novo validations also demonstrate the ability of EdgCSN in predicting new disease genes.ConclusionsIn this study, we propose EdgCSN, which is an ensemble learning algorithm for predicting disease genes with models trained by centrality features extracted from clinical sample-based networks. Results of the leave-one-out cross validation show that our EdgCSN performs much better than the competing algorithms in predicting BC-associated, TC-associated and AD-associated genes. de novo validations also show that EdgCSN is valuable for identifying new disease genes.

A novel graph clustering method with a greedy heuristic search algorithm for mining protein complexes from dynamic and static PPI networks

Discovering protein complexes from protein-protein interaction (PPI) networks is one of the primary tasks in bioinformatics. However, most of the state-of-the-art methods still face some challenges, such as the inability to discover overlapping protein complexes, failure to consider the inherent structure of real protein complexes, and non-utilization of biological information. Based on the above mentioned aspects, we present a novel graph clustering method with a greedy heuristic search algorithm for mining protein complexes using a new clustering model in dynamic and static weighted PPI networks (named MPC-C). First, MPC-C constructed dynamic and static weighted PPI networks by combining biological and topological information. Second, initial clusters were obtained using core and multifunctional proteins, following which we proposed a greedy heuristic search algorithm to expand each initial cluster and form candidate protein complexes in dynamic and static weighted PPI networks. Finally, unreliable and highly overlapping protein complexes were discarded. To demonstrate the performance of MPC-C, we tested this method on five PPI networks and compared it with nine other effective methods. The experimental results indicate that MPC-C outperformed the other state-of-the-art methods with respect to various computational and biologically relevant metrics.

Detection of dynamic protein complexes through Markov Clustering based on Elephant Herd Optimization Approach

The accessibility of a huge amount of protein-protein interaction (PPI) data has allowed to do research on biological networks that reveal the structure of a protein complex, pathways and its cellular organization. A key demand in computational biology is to recognize the modular structure of such biological networks. The detection of protein complexes from the PPI network, is one of the most challenging and significant problems in the post-genomic era. In Bioinformatics, the frequently employed approach for clustering the networks is Markov Clustering (MCL). Many of the researches for protein complex detection were done on the static PPI network, which suffers from a few drawbacks. To resolve this problem, this paper proposes an approach to detect the dynamic protein complexes through Markov Clustering based on Elephant Herd Optimization Approach (DMCL-EHO). Initially, the proposed method divides the PPI network into a set of dynamic subnetworks under various time points by combining the gene expression data and secondly, it employs the clustering analysis on every subnetwork using the MCL along with Elephant Herd Optimization approach. The experimental analysis was employed on different PPI network datasets and the proposed method surpasses various existing approaches in terms of accuracy measures. This paper identifies the common protein complexes that are expressively enriched in gold-standard datasets and also the pathway annotations of the detected protein complexes using the KEGG database.

A method for identifying protein complexes with the features of joint co-localization and joint co-expression in static PPI networks

Identifying protein complexes in static protein-protein interaction (PPI) networks is essential for understanding the underlying mechanism of biological processes. Proteins in a complex are co-localized at the same place and co-expressed at the same time. We propose a novel method to identify protein complexes with the features of joint co-localization and joint co-expression in static PPI networks. To achieve this goal, we define a joint localization vector to construct a joint co-localization criterion of a protein group, and define a joint gene expression to construct a joint co-expression criterion of a gene group. Moreover, the functional similarity of proteins in a complex is an important characteristic. Thus, we use the CC-based, MF-based, and BP-based protein similarities to devise functional similarity criterion to determine whether a protein is functionally similar to a protein cluster. Based on the core-attachment structure and following to seed expanding strategy, we use four types of biological data including PPI data with reliability score, protein localization data, gene expression data, and gene ontology annotations, to identify protein complexes. The experimental results on yeast data show that comparing with existing methods our proposed method can efficiently and exactly identify more protein complexes, especially more protein complexes of sizes from 2 to 6. Furthermore, the enrichment analysis demonstrates that the protein complexes identified by our method have significant biological meaning.

PCD-DPPI: Protein complex detection from dynamic PPI using shuffled frog-leaping algorithm

In the post-genome period, the identification of a protein complex from large PPI (protein-protein interaction) networks is a challenging task. Protein complexes plays a vital character in numerous molecular processes of the cell. Although, the maximum computational techniques of protein complex detection have aimed at static PPI networks that cannot represent the logical dynamicity of protein interactions. In recent times, the dynamicity of PPI networks has been exploited by building a set of dynamic PPI subnetworks with respect to every time-point in a gene expression matrix. This paper presents a new technique, called Protein Complex Detection based on Dynamic PPI (PCD-DPPI) to accomplish dynamicity in protein complex detection. The initial stage of the proposed technique is based on shuffled frog-leaping algorithm, an Optimization technique that take out a few sets of genes that are co-regulated beneath some conditions from the input gene expression matrix. An individual extracted gene set is defined as a bicluster. In the second stage, depending on the biclusters, few dynamic PPI subnetworks are taken out from the input static PPI network. By employing a complex detection approach on every dynamic PPI subnetworks, protein complexes are identified and the result is aggregated. The proposed and existing algorithms were applied to various datasets such as DIP, Krogan “Extended”, Krogan “Core”, Gavin2, Gavin6, PPI 1, Collins and Gavin + Krogan. Experimental results have been proved that the proposed PCD-DPPI efficiently depicts the dynamicity characteristics in static PPI networks and attains expressively better results when compared to other existing standard methods.

A Method for Predicting Protein Complexes from Dynamic Weighted Protein-Protein Interaction Networks.

Predicting protein complexes from protein-protein interaction (PPI) network is of great significance to recognize the structure and function of cells. A protein may interact with different proteins under different time or conditions. Existing approaches only utilize static PPI network data that may lose much temporal biological information. First, this article proposed a novel method that combines gene expression data at different time points with traditional static PPI network to construct different dynamic subnetworks. Second, to further filter out the data noise, the semantic similarity based on gene ontology is regarded as the network weight together with the principal component analysis, which is introduced to deal with the weight computing by three traditional methods. Third, after building a dynamic PPI network, a predicting protein complexes algorithm based on "core-attachment" structural feature is applied to detect complexes from each dynamic subnetworks. Finally, it is revealed from the experimental results that our method proposed in this article performs well on detecting protein complexes from dynamic weighted PPI networks.

CPredictor3.0: detecting protein complexes from PPI networks with expression data and functional annotations

BackgroundEffectively predicting protein complexes not only helps to understand the structures and functions of proteins and their complexes, but also is useful for diagnosing disease and developing new drugs. Up to now, many methods have been developed to detect complexes by mining dense subgraphs from static protein-protein interaction (PPI) networks, while ignoring the value of other biological information and the dynamic properties of cellular systems.ResultsIn this paper, based on our previous works CPredictor and CPredictor2.0, we present a new method for predicting complexes from PPI networks with both gene expression data and protein functional annotations, which is called CPredictor3.0. This new method follows the viewpoint that proteins in the same complex should roughly have similar functions and are active at the same time and place in cellular systems. We first detect active proteins by using gene express data of different time points and cluster proteins by using gene ontology (GO) functional annotations, respectively. Then, for each time point, we do set intersections with one set corresponding to active proteins generated from expression data and the other set corresponding to a protein cluster generated from functional annotations. Each resulting unique set indicates a cluster of proteins that have similar function(s) and are active at that time point. Following that, we map each cluster of active proteins of similar function onto a static PPI network, and get a series of induced connected subgraphs. We treat these subgraphs as candidate complexes. Finally, by expanding and merging these candidate complexes, the predicted complexes are obtained.We evaluate CPredictor3.0 and compare it with a number of existing methods on several PPI networks and benchmarking complex datasets. The experimental results show that CPredictor3.0 achieves the highest F1-measure, which indicates that CPredictor3.0 outperforms these existing method in overall.ConclusionCPredictor3.0 can serve as a promising tool of protein complex prediction.

An uncertain model-based approach for identifying dynamic protein complexes in uncertain protein-protein interaction networks

BackgroundRecently, researchers have tried to integrate various dynamic information with static protein-protein interaction (PPI) networks to construct dynamic PPI networks. The shift from static PPI networks to dynamic PPI networks is essential to reveal the cellular function and organization. However, it is still impossible to construct an absolutely reliable dynamic PPI networks due to the noise and incompletion of high-throughput experimental data.ResultsTo deal with uncertain data, some uncertain graph models and theories have been proposed to analyze social networks, electrical networks and biological networks. In this paper, we construct the dynamic uncertain PPI networks to integrate the dynamic information of gene expression and the topology information of high-throughput PPI data. The dynamic uncertain PPI networks can not only provide the dynamic properties of PPI, which are neglected by static PPI networks, but also distinguish the reliability of each protein and PPI by the existence probability. Then, we use the uncertain model to identify dynamic protein complexes in the dynamic uncertain PPI networks.ConclusionWe use gene expression data and different high-throughput PPI data to construct three dynamic uncertain PPI networks. Our approach can achieve the state-of-the-art performance in all three dynamic uncertain PPI networks. The experimental results show that our approach can effectively deal with the uncertain data in dynamic uncertain PPI networks, and improve the performance for protein complex identification.

Neighbor Affinity-Based Core-Attachment Method to Detect Protein Complexes in Dynamic PPI Networks.

Protein complexes play significant roles in cellular processes. Identifying protein complexes from protein-protein interaction (PPI) networks is an effective strategy to understand biological processes and cellular functions. A number of methods have recently been proposed to detect protein complexes. However, most of methods predict protein complexes from static PPI networks, and usually overlook the inherent dynamics and topological properties of protein complexes. In this paper, we proposed a novel method, called NABCAM (Neighbor Affinity-Based Core-Attachment Method), to identify protein complexes from dynamic PPI networks. Firstly, the centrality score of every protein is calculated. The proteins with the highest centrality scores are regarded as the seed proteins. Secondly, the seed proteins are expanded to complex cores by calculating the similarity values between the seed proteins and their neighboring proteins. Thirdly, the attachments are appended to their corresponding protein complex cores by comparing the affinity among neighbors inside the core, against that outside the core. Finally, filtering processes are carried out to obtain the final clustering result. The result in the DIP database shows that the NABCAM algorithm can predict protein complexes effectively in comparison with other state-of-the-art methods. Moreover, many protein complexes predicted by our method are biologically significant.

Dynamic protein–protein interaction networks construction using firefly algorithm

Protein–protein interaction (PPI) networks are dynamic in the real world. That is, at different times and under different conditions, the interaction among proteins may or may not be active. In different dataset, PPI networks might be gathered as static or dynamic networks. For the conversion of static PPI networks to time graphs, i.e., dynamic PPI networks, additional information like gene expression and gene co-expression profiles is used. One of the challenges in system biology is to determine appropriate thresholds for converting static PPI networks to dynamic PPI networks based on active proteins. In the available methods, fixed thresholds are used for all genes. However, the purpose of this study is to determine an adaptive unique threshold for each gene. In this study, the available additional information at different times and conditions and gold-standard protein complexes was employed to determine fitting thresholds. By so doing, the problem is converted into an optimization problem. Thereafter, the problem is solved using the firefly meta-heuristic optimization algorithm. One of the most remarkable aspects of this study is determining the attractiveness function in the firefly algorithm. In this study, attraction is defined as a combination of standard complexes and gene co-expressions. Then, active proteins are specified utilizing the created thresholds. The MCL, ClusterOne, MCODE and Coach algorithms are used for final evaluation. The experimental results about BioGRID dataset and CYC2008 gold-standard protein complexes indicated that the produced dynamic PPI networks by the proposed method have better results than the earlier methods.

Weighted edge based clustering to identify protein complexes in protein–protein interaction networks incorporating gene expression profile

Protein complex detection from protein–protein interaction (PPI) network has received a lot of focus in recent years. A number of methods identify protein complexes as dense sub-graphs using network information while several other methods detect protein complexes based on topological information. While the methods based on identifying dense sub-graphs are more effective in identifying protein complexes, not all protein complexes have high density. Moreover, existing methods focus more on static PPI networks and usually overlook the dynamic nature of protein complexes. Here, we propose a new method, Weighted Edge based Clustering (WEC), to identify protein complexes based on the weight of the edge between two interacting proteins, where the weight is defined by the edge clustering coefficient and the gene expression correlation between the interacting proteins. Our WEC method is capable of detecting highly inter-connected and co-expressed protein complexes. The experimental results of WEC on three real life data shows that our method can detect protein complexes effectively in comparison with other highly cited existing methods.Availability: The WEC tool is available at http://agnigarh.tezu.ernet.in/~rosy8/shared.html.

BiCAMWI: A Genetic-Based Biclustering Algorithm for Detecting Dynamic Protein Complexes.

Considering the roles of protein complexes in many biological processes in the cell, detection of protein complexes from available protein-protein interaction (PPI) networks is a key challenge in the post genome era. Despite high dynamicity of cellular systems and dynamic interaction between proteins in a cell, most computational methods have focused on static networks which cannot represent the inherent dynamicity of protein interactions. Recently, some researchers try to exploit the dynamicity of PPI networks by constructing a set of dynamic PPI subnetworks correspondent to each time-point (column) in a gene expression data. However, many genes can participate in multiple biological processes and cellular processes are not necessarily related to every sample, but they might be relevant only for a subset of samples. So, it is more interesting to explore each subnetwork based on a subset of genes and conditions (i.e., biclusters) in a gene expression data. Here, we present a new method, called BiCAMWI to employ dynamicity in detecting protein complexes. The preprocessing phase of the proposed method is based on a novel genetic algorithm that extracts some sets of genes that are co-regulated under some conditions from input gene expression data. Each extracted gene set is called bicluster. In the detection phase of the proposed method, then, based on the biclusters, some dynamic PPI subnetworks are extracted from input static PPI network. Protein complexes are identified by applying a detection method on each dynamic PPI subnetwork and aggregating the results. Experimental results confirm that BiCAMWI effectively models the dynamicity inherent in static PPI networks and achieves significantly better results than state-of-the-art methods. So, we suggest BiCAMWI as a more reliable method for protein complex detection.

A method for predicting protein complex in dynamic PPI networks.

BackgroundAccurate determination of protein complexes has become a key task of system biology for revealing cellular organization and function. Up to now, the protein complex prediction methods are mostly focused on static protein protein interaction (PPI) networks. However, cellular systems are highly dynamic and responsive to cues from the environment. The shift from static PPI networks to dynamic PPI networks is essential to accurately predict protein complex.ResultsThe gene expression data contains crucial dynamic information of proteins and PPIs, along with high-throughput experimental PPI data, are valuable for protein complex prediction. Firstly, we exploit gene expression data to calculate the active time point and the active probability of each protein and PPI. The dynamic active information is integrated into high-throughput PPI data to construct dynamic PPI networks. Secondly, a novel method for predicting protein complexes from the dynamic PPI networks is proposed based on core-attachment structural feature. Our method can effectively exploit not only the dynamic active information but also the topology structure information based on the dynamic PPI networks.ConclusionsWe construct four dynamic PPI networks, and accurately predict many well-characterized protein complexes. The experimental results show that (i) the dynamic active information significantly improves the performance of protein complex prediction; (ii) our method can effectively make good use of both the dynamic active information and the topology structure information of dynamic PPI networks to achieve state-of-the-art protein complex prediction capabilities.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1101-y) contains supplementary material, which is available to authorized users.

Construction of dynamic probabilistic protein interaction networks for protein complex identification.

BackgroundRecently, high-throughput experimental techniques have generated a large amount of protein-protein interaction (PPI) data which can construct large complex PPI networks for numerous organisms. System biology attempts to understand cellular organization and function by analyzing these PPI networks. However, most studies still focus on static PPI networks which neglect the dynamic information of PPI.ResultsThe gene expression data under different time points and conditions can reveal the dynamic information of proteins. In this study, we used an active probability-based method to distinguish the active level of proteins at different active time points. We constructed dynamic probabilistic protein networks (DPPN) to integrate dynamic information of protein into static PPI networks. Based on DPPN, we subsequently proposed a novel method to identify protein complexes, which could effectively exploit topological structure as well as dynamic information of DPPN. We used three different yeast PPI datasets and gene expression data to construct three DPPNs. When applied to three DPPNs, many well-characterized protein complexes were accurately identified by this method.ConclusionThe shift from static PPI networks to dynamic PPI networks is essential to accurately identify protein complex. This method not only can be applied to identify protein complex, but also establish a framework to integrate dynamic information into static networks for other applications, such as pathway analysis.

Protein Complex Detection in PPI Network by Identifying Mutually Exclusive Protein-protein Interactions

Identifying protein complexes within Protein-Protein Interaction Networks (PPINs) is an important task in computational biology for analyzing biological processes and pathways. A protein complex can be represented as a group of two or more interacting proteins that formed a dense sub-graph in PPIN. In PPIN, it also corresponds to a cluster of proteins which not only includes interactions that are stable over time, but it also includes dynamic interactions. Two interactions are dynamic if they are mutually exclusive. Conventional protein complex detection approach used graph theoretic clustering methods on static PPI data and disregard the dynamic interaction. In this paper, we have proposed a multiobjective framework that considers interaction dynamics for detecting protein complexes. The framework is motivated by an widely used protein complex detection method called PROCOMOSS 1 that is used in static PPI data. The performance of the proposed framework is compared with other state-of-the-art techniques for both static and dynamic PPI data separately. The results show a significant improvement in the matching statistics over static PPIN. We have also performed a gene ontology and pathway based analysis of the resulting protein complexes.

Improving Identification of Key Players in Aging via Network De-Noising and Core Inference.

Current "ground truth" knowledge about human aging has been obtained by transferring aging-related knowledge from well-studied model species via sequence homology or by studying human gene expression data. Since proteins function by interacting with each other, analyzing protein-protein interaction (PPI) networks in the context of aging is promising. Unlike existing static network research of aging, since cellular functioning is dynamic, we recently integrated the static human PPI network with aging-related gene expression data to form dynamic, age-specific networks. Then, we predicted as key players in aging those proteins whose network topologies significantly changed with age. Since current networks are noisy , here, we use link prediction to de-noise the human network and predict improved key players in aging from the de-noised data. Indeed, de-noising gives more significant overlap between the predicted data and the "ground truth" aging-related data. Yet, we obtain novel predictions, which we validate in the literature. Also, we improve the predictions by an alternative strategy: removing "redundant" edges from the age-specific networks and using the resulting age-specific network "cores" to study aging. We produce new knowledge from dynamic networks encompassing multiple data types, via network de-noising or core inference, complementing the existing knowledge obtained from sequence or expression data.