Documentation and Help



Bioplex 2.0 Background

Architecture of the human interactome defines protein communities and disease networks:
The physiology of a cell can be viewed as the product of thousands of proteins acting in concert to shape the cellular response. Coordination is achieved in part through networks of protein-protein interactions that assemble functionally related proteins into complexes, organelles, and signal transduction pathways. Understanding the architecture of the human proteome has the potential to inform cellular, structural, and evolutionary mechanisms and is critical to elucidating how genome variation contributes to disease. Here we present BioPlex 2.0 (Biophysical Interactions of ORFeome-derived complexes), which uses robust affinity purification-mass spectrometry methodology to elucidate protein interaction networks and co-complexes nucleated by more than 25% of protein-coding genes from the human genome, and constitutes, to our knowledge, the largest such network so far. With more than 56,000 candidate interactions, BioPlex 2.0 contains more than 29,000 previously unknown co-associations and provides functional insights into hundreds of poorly characterized proteins while enhancing network-based analyses of domain associations, subcellular localization, and co-complex formation. Unsupervised Markov clustering of interacting proteins identified more than 1,300 protein communities representing diverse cellular activities. Genes essential for cell fitness are enriched within 53 communities representing central cellular functions. Moreover, we identified 442 communities associated with more than 2,000 disease annotations, placing numerous candidate disease genes into a cellular framework. BioPlex 2.0 exceeds previous experimentally derived interaction networks in depth and breadth, and will be a valuable resource for exploring the biology of incompletely characterized proteins and for elucidating larger-scale patterns of proteome organization.

Please Cite:
Latest BioPlex Manuscript: Huttlin et. al. Nature (2017)
BioPlexDisplay Manuscript: Schweppe et. al. JPR (2018)



Contact Information

The BioPlex Display website was developed by Devin K. Schweppe, Edward L. Huttlin, J. Wade Harper and Steve P. Gygi.

For questions pertaining to the website please email Devin K Schweppe at:

devin_schweppe at hms dot harvard dot edu
(bolded portions should be symbols).

For other comments or questions, please see the Links and People pages for more information.






External Queries of Protein Interactions Networks

Proteins of interest can also be queries externally using the following link:

bioplex.hms.harvard.edu/bioplexDisplay/externalQuery.php?geneQuery=<geneID>

Where <geneID> should be a gene ID number for the protein of interest.

Examples:
Bin3: bioplex.hms.harvard.edu/bioplexDisplay/externalQuery.php?geneQuery=55909
EGFR: bioplex.hms.harvard.edu/bioplexDisplay/externalQuery.php?geneQuery=1956


Access data through the BioPlex API

Interactions can be queried through an API for access to the protein-protein interaction data underlying the BioPlex Display site. Data can be exported as either JSON arrays (default) or tab-seperated flat files (.txt).

The API will not export queries larger than 25000 rows. If you need the full dataset, please download that here.

Potential query parameters:

geneQuery - Query all interactions involving a specific geneID.
pintLow - Low probability of interaction filter. Interactions with probability of interaction greater than or equal to this value will be extracted.
pintHigh - High probability of interaction filter. Interactions with probability of interaction less than or equal to this value will be extracted.
interaction - Query BioPlex for a specific interaction (geneID-geneID).

Examples:
Bin3 Interactions (JSON Array):
http://bioplex.hms.harvard.edu/bioplexDisplay/api/api.php?geneQuery=55909
Bin3 Interactions (TXT):
http://bioplex.hms.harvard.edu/bioplexDisplay/api/api.php?geneQuery=55909&json=0
EGFR Interactions (JSON Array):
http://bioplex.hms.harvard.edu/bioplexDisplay/api/api.php?geneQuery=1956
EGFR Interactions (0.9 < pInt < 1, JSON Array):
http://bioplex.hms.harvard.edu/bioplexDisplay/api/api.php?geneQuery=1956&pintLow=0.9&pintHigh=1
EGFR-PTPRK Interaction (JSON Array):
http://bioplex.hms.harvard.edu/bioplexDisplay/api/api.php?interaction=1956-5796


Protein Community Query

BioPlex Display enables users to query protein communities from within the full interaction network.



Protein Community Display

These tightly connected sub-networks represent specific protein complexes and protein pathway interactions. Furthermore, users are enabled to query proteins of interest against these communities from the Display homepage.

Example of the community containing Taf2:


Network Toolbar

BioPlex sub-networks are displayed using Cytoscape.js. Within each display there are multiple options for exploring the BioPlex interactions with your protein interest. Nodes can be selected using CTRL+click-and-drag.

  1. Core Network Display
  2. Interactions
  3. Network Search
  4. Layouts
  5. Coloring
  6. GO Annotation Enrichment
  7. GO Annotation Coloring
  8. Node and Edge Info.
  9. Zoom
  10. Export Data
  11. Interaction Table

Core Network Display

For display purposes the "core network" or "core sub-network" refer to the protein-of-interest (selected on the home page search) and any other protein observed in a direct interaction with said protein-of-interest.

The below network shows the MED10 Core Network:




Interactions

This dropdown menu allows users to add, select and remove nodes according to several criteria.




First Neighbor Interactions

Users can use this feature to select all first neighbor nodes for a protein of interest. This feature can help to identify proteins interactions of interest in large networks (e.g. secondary networks or community networks).




Secondary Interactions

For each core sub-network, users can add secondary interactions. These secondary proteins do no directly interact with the original protein of interest, but interact with the original protein's interactors.

Additionally, adding Secondary Interactions will update the Gene Ontoogy Enrichment table.




Sub-threshold Interactions

Users can add a subset of AP-MS identified interactions that fall below the threshold (probability of interaction = 0.75) necessary to be considered an true interaction in the BioPlex dataset.
Important these interactions are NOT part of the final, statistically-filtered BioPlex interactome and should not be viewed or used as such.




Network Search

Within either the core or secondary networks individual proteins can be highlighted in the "Search in Network" input bar.
This search bar will accept and try to match protein symbols, gene ID numbers, and Uniprot Accession numbers. If the requisite node exists in the network it will be highlighted.




Layouts

Each network graph can be displayed using a number of different layouts (e.g. grid, spring embedded, circular).




Coloring

Each network can be recolored based on protein attributes. Currently, this includes coloring nodes by their abundance in HEK293 cells, and by their GO/PFAM annotations. To color by HEK293 abundance, click the "Coloring" dropdown menu above the network and select "HEK293 Coloring".

HEK293 Abundance:





GO Annotation Enrichment

Each sub-network within the Bioplex network is automatically tested for Gene Ontology (GO) enrichment based on the Fisher's Exact Test, adjusted based on the Benjamini-Hochberg FDR. Annotations with an FDR less than 0.001 are highlighted in the GO Annotation Table and the top 4 GO annotations from each network that pass the 0.001 FDR threshold are displayed next to each graph.

We note that all GO Enrichments (both primary and secondary networks) are calculated based on the proteins in a network with a probability of interaction greater than or equal to 0.75.




GO Annotation Coloring

By clicking on enriched GO annotation, the proteins associated with the GO term will be highlighted and the highlighed annotation name will be overlaid on the network.




Node and Edge Information

More information for both the nodes and the edges can be obtained by clicking on either the node or edge. This includes links to Uniprot references for each protein and the probability of interaction for each edge.

Node:

Edge:





Zoom

The viewport can be adjusted by zooming to fit or zooming to the selected nodes.




Interaction Table

Node information from the core network can be found in the node table at the bottom of each page. Clicking the protein symbol will highlight the protein within the network. Clicking the Uniprot Accessions links out the Uniprot.




Export Data

Networks can be exported as either a flat text file containing all interaction information for the sub-network, a PNG displaying the network (either the original image or the current one), or as a JSON file that can be directly imported into Cytoscape to further explore the data.

PLEASE NOTE:
Very large networks can cause the PNG image export to fail. If your download does not succeed at first, please try to reduce the size of the network canvas (bottom left corner).




©2017 Gygi Lab & The President and Fellows of Harvard College