- CONDOR
- ALPACA
- CRANE

CONDOR is a tool for community detection in bipartite networks. Many community detection methods for unipartite networks are based on the concept of maximizing a modularity metric that compares the weight of edges within communities to the weight of edges between communities, prioritizing community assignments with higher values of the former relative to the latter. CONDOR extends this concept to bipartite networks by optimizing a bipartite version of modularity defined by Barber (2007). To enable bipartite community detection on large networks such gene regulatory networks, CONDOR uses a fast unipartite modularity maximization method on one of the two unipartite projections of the bipartite network. In Platig et al. (2016), CONDOR is applied to bipartite networks of single nucleotide polymorphisms (SNPs) and gene expression, where a network edge from a SNP node to a gene node is indicative of an association between the SNP and the gene expression level, commonly known as an expression quantitative trait locus (eQTL). Communities detected with CONDOR contained local hub nodes (core SNPs) enriched for association with disease, suggesting that functional eQTL relationships are encoded at the community level.

ALPACA is a method for differential network analysis that is based on a novel approach to comparison of network community structures. Comparisons of community structure have typically been accomplished by assessing which nodes switch community membership between networks (community comparison) or by computing the edge weight differences by subtracting the adjacency matrices of two networks and then performing community detection on the resulting differential network (edge subtraction). Both these approaches have important limitations. Community comparison is subject to a resolution limit and cannot detect differences smaller than the average community size in a network. Edge subtraction transfers noise from both of the original networks to the differential network, leading to an imprecise estimator. Moreover, positive and negative edge differences cannot be distinguished in the subsequent community detection performed on the differential network. In contrast to community comparison and edge subtraction, ALPACA compares the community structure of two networks by optimizing a new metric: differential modularity. In the ALPACA algorithm, one network is defined as the reference network and the second is defined as the perturbed network. The differential modularity metric measures the extent to which edges in a community in the perturbed network differ from those that would be expected by random chance according to a null distribution based on the reference network. Community structure of the perturbed network is determined by maximizing this differential modularity. The resulting communities are differential modules that show how the perturbed network differs from the reference network at the community level.

CRANE is a method for determining statistical significance of structural differences between networks. Analysis with CRANE is a four-phase process. The first step of CRANE is to estimate two networks: a reference network and a perturbed network. In the same spirit as LIONESS, CRANE is flexible: any network inference method (e.g., correlation, partial correlation, PANDA) can be used at this stage. In the second step, differential features are determined by comparing the reference and perturbed networks. Here, CRANE is again flexible: such differential features could arise from simple measures such as a comparison of node degree or centrality, or from more nuanced techniques such as differential module detection with ALPACA. Third, a large number of constrained random networks are developed based on the network structure of the reference network. By comparing each random network with the original reference network, a set of null differential measures is obtained. Fourth, the observed differential features from step two can be compared with the null distribution from step three to generate empirical p-values. A typical workflow for applying CRANE in NetZooR would involve fitting PANDA networks in step one and using ALPACA to estimate differential modules in step two.