Performance Assessment of the Network Reconstruction Approaches on Various Interactomes

Beyond the list of molecules, there is a necessity to collectively consider multiple sets of omic data and to reconstruct the connections between the molecules. Especially, pathway reconstruction is crucial to understanding disease biology because abnormal cellular signaling may be pathological. The main challenge is how to integrate the data together in an accurate way. In this study, we aim to comparatively analyze the performance of a set of network reconstruction algorithms on multiple reference interactomes. We first explored several human protein interactomes, including PathwayCommons, OmniPath, HIPPIE, iRefWeb, STRING, and ConsensusPathDB. The comparison is based on the coverage of each interactome in terms of cancer driver proteins, structural information of protein interactions, and the bias toward well-studied proteins. We next used these interactomes to evaluate the performance of network reconstruction algorithms including all-pair shortest path, heat diffusion with flux, personalized PageRank with flux, and prize-collecting Steiner forest (PCSF) approaches. Each approach has its own merits and weaknesses. Among them, PCSF had the most balanced performance in terms of precision and recall scores when 28 pathways from NetPath were reconstructed using the listed algorithms. Additionally, the reference interactome affects the performance of the network reconstruction approaches. The coverage and disease- or tissue-specificity of each interactome may vary, which may result in differences in the reconstructed networks.

Node-weighted Network Design in Planar and Minor-closed Families of Graphs

We consider node-weighted survivable network design (SNDP) in planar graphs and minor-closed families of graphs. The input consists of a node-weighted undirected graph G = ( V , E ) and integer connectivity requirements r ( uv ) for each unordered pair of nodes uv . The goal is to find a minimum weighted subgraph H of G such that H contains r ( uv ) disjoint paths between u and v for each node pair uv . Three versions of the problem are edge-connectivity SNDP (EC-SNDP), element-connectivity SNDP (Elem-SNDP), and vertex-connectivity SNDP (VC-SNDP), depending on whether the paths are required to be edge, element, or vertex disjoint, respectively. Our main result is an O ( k )-approximation algorithm for EC-SNDP and Elem-SNDP when the input graph is planar or more generally if it belongs to a proper minor-closed family of graphs; here, k = max uv r ( uv ) is the maximum connectivity requirement. This improves upon the O ( k log n )-approximation known for node-weighted EC-SNDP and Elem-SNDP in general graphs [31]. We also obtain an O (1) approximation for node-weighted VC-SNDP when the connectivity requirements are in {0, 1, 2}; for higher connectivity our result for Elem-SNDP can be used in a black-box fashion to obtain a logarithmic factor improvement over currently known general graph results. Our results are inspired by, and generalize, the work of Demaine, Hajiaghayi, and Klein [13], who obtained constant factor approximations for node-weighted Steiner tree and Steiner forest problems in planar graphs and proper minor-closed families of graphs via a primal-dual algorithm.

CytoTalk: De novo construction of signal transduction networks using single-cell transcriptomic data

Single-cell technology enables study of signal transduction in a complex tissue at unprecedented resolution. We describe CytoTalk for de novo construction of cell type–specific signaling networks using single-cell transcriptomic data. Using an integrated intracellular and intercellular gene network as the input, CytoTalk identifies candidate pathways using the prize-collecting Steiner forest algorithm. Using high-throughput spatial transcriptomic data and single-cell RNA sequencing data with receptor gene perturbation, we demonstrate that CytoTalk has substantial improvement over existing algorithms. To better understand plasticity of signaling networks across tissues and developmental stages, we perform a comparative analysis of signaling networks between macrophages and endothelial cells across human adult and fetal tissues. Our analysis reveals an overall increased plasticity of signaling networks across adult tissues and specific network nodes that contribute to increased plasticity. CytoTalk enables de novo construction of signal transduction pathways and facilitates comparative analysis of these pathways across tissues and conditions.