SPARK

The SPARK: Sensor Proteome Alliance for DNA Repair and Kinetics, is an Israel-based resourse hosted by Professor Dr Deborah Toiber and the Ben-Gurion University of the Negev. The resource was initiated in 2025 with the aim of generate a dynamic and comprehensive mapping of the protein protein interactions of the main DSB sensor proteins thtough the repair of DNA double strand breaks. The resource include the proteomic and network analysis results of the interactomes of three DSB sensor proteins, Mre11, Ku80, and Sirt6, at several time points of the DNA Damage response. The experimental and analytical procedures were throughly described in the original article (Garcia-Venzor, et al., 2025* hopefully). All the data in the SPARK Sensor Proteome Alliance for DNA Repair and Kinetics is open access to allow scientists and students in academia or in the private sector to freely access the data for the exploration of the DSB Sensor protein interactome.

The SPARK resource contains three separated modules:

1. The full network: The full network contain all the protein interactors found at each specific time points and the reported interactions that occurs among them and the DSB sensor protein. The interactions information was retrieved from the curated set of physical interactions from the String database [1]. This option retrieves the high-resolution images of the full networks, where each node corresponds to a protein and each edge to a String database curated physical interaction. Two filtering options are available: The type of network to display refers to the node coloring system used, whether it will be based on the structural modules or the annotated nuclear roles. The time point refers to the experimental post-irradiation stage where the networks belong. Furthermore, the full network module allow the user to download the entire proteome database with the quantitative and network analysis measurements for all the proteins, or by specific functional set of proteins.
2. Protein Query: The SPARK database can be also explored by protein. This module allow the user to find specific proteins in the database and retrieve its information. The information displayed for each protein can be downloaded as independent files for each measurements and as graphics with the heatmaps as displayed in the web page. The information that can be searched is:
   1. The general information of the protein and its description. Obtained from the Uniprot database [2], and the String database [1]. The functional annotation that was curated from the Gene ontology functional annotations for that protein [3, 4].
   2. The binding fold change. Which is the Log2Fold Change calculated by the Limma T-test against the background signal (experimental negative control), in each time point and in each DSB sensor protein. If a Fold Change value is missing in a specific time point, it means that the protein interaction was not detected in that particular time point.
   3. Specificity: It contains the information regarding if an interactor is specific for a particular DSB sensir protein interactome or if it is shared between the interactomes of two or more DSB sensor proteins. It contains two measurements, the multivariate analysis modelling by OPLS-DA that models the variances of the proteins, and calculates the correlation and covariance of one protein with a particular DSB sensor protein, and a classical Venn set analysis of the composition of the time specific interactomes. Both parameters can be used to asses the specificity of the protein interactors.
   4. Networks Metrics and node classification: In this section several network metrics are displayed for the queried protein. The degree refers to the number of interactions that the queried protein has in a particular time point. The Connectivity, refers to the normalized amount of intra-module interactions the queried protein has. The Participation, refers to the normalized amount of inter-module interactions the queried protein presents. The Module, refers to the structural module it belongs to, and the role refers to the connectivity role of the protein. Proteins with high participation are classfied as connector proteins, while proteins with high connectivity are classified as module hubs.
3. The Queried proteins PPI networks: This section will contain small sub-networks that show all the Protein-protein interactions of the queried protein in each specific time point and in each specific DSB sensor protein. The node coloring is based on the core functions, as stated in the main original article (Garcia-Venzor, et al., 2025*hopefully). The specific time point has to be selected, and the nonIR condition is set as the default. If the queried protein is not present in the selected time point, the network will show only the disconnected node of that protein without any interactor. The sub-networks can be downloaded as edgelist, or graphs of the networks.