### Supplementary

• S1. Equations of Algorithms used in this plug-in

• Local-based Methods
Here we state notations used for describing these methods. We assume that a biological network G = (V, E) is an undirected network, where V is the collection of nodes within the network and E is the edge set. We can use another notation G = (V(G), E(G))) to represent a network, where V(G) is the collection of nodes in a network G, and E(G) is the collection of edges in a network G. For a set S, we use |S| to denote its cardinality (i.e. the number of elements in the set). Local based method only considers the direct neighborhood of a node. Given a node v, N(v) denotes the collections of its neighbors. There are four local based methods shown as follows:
MethodsDefinitions
Degree method (Deg) deg(v)=|N(v)|
Maximum Neighborhood Component (MNC) MNC(v) = |V(MC(v))| , where MC(v) is a maximum connected component of the G[N(v)] and G[N(v)] is the induced subgraph of G by N(v).
Density of Maximum Neighborhood Component (DMNC) DMNC(v) = |E(MC(v))|/ |V(MC(v))|ε, where ε=1.7.
Maximal Clique Centrality (MCC)
, where S(v) is the collection of maximal cliques which contain v , and (|C|-1)! is the product of all positive integers less than |C|.

• Global-based Methods
In cytoHubba we implement six node ranking methods based on shortest paths and one method based percolated connectivity. Before we introduce the shortest based methods, let us introduce some notation. The length of a shortest path between nodes u and v is denoted as dist(u, v).
MethodsDefinitions
Closeness (Clo)
EcCentricity (EC)
BottleNeck (BN)
Stress (Str)
Betweenness (BC)
Edge Percolated Component (EPC)

• S2. Networks used in this study

• S3. Essential protein list

• S4. Dependence among different methods (Take result from yeast as example, observation is the percentage of common proteins in top 100 ranked lists of every pair of scoring methods)

• S5. The prediction on yeast essential proteins

• S6. (A) A cytoHubba analysis result using the example dataset galFiltered.cys in the Cytoscape. After the calculation, top 10 essential nodes ranked by MCC scores were selected from the yeast network. (B) Node and edge annotations are accessible through Cytoscape Data Panel.