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Viruses in the News


Academic year: 2022

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A Prototype of the HumanVirus Interact ome Resource (HVIR)

Tax1 Binds toBinds to Protein B

Interacts with Interacts with Co-Co-localizes withlocalizes with Co-Co-purifies withpurifies with

Forms a complex with Forms a complex with


Alex Pothen M. Zubair Kurt Maly

Chris Osgood John



Viruses in the News

• HIV, SARS, Avian Flu, Human flu pandemics

• A virus conjectured to be cause of

mammalian extinctions in the Pleistocene

• Viral proteins interacting with human

proteins are responsible for infection and transmission; targets for therapies

• Currently no automated tools to mine

published viral-human protein interactions


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Coping with Growing Proteomic Information

• Recent advances in protein science

– High throughput experimental methodologies: Yeast 2-hybrid system, Tagged affinity purification, etc.

• On-line literature and protein interactions

databases growing rapidly (>16 Million abstracts in PubMed)

• Need for automated tools to aggregate data, process it, and present it visually in biologically meaningful ways

• Need standards for representing data, and tools that support interoperable databases


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The HVIR Framework

Viral-human protein interactions mined from the literature, e.g., PubMed

Human interactome from curated databases, e.g., Human Protein Reference Database (HPRD)

Integrate the data into a repository, HVIR

– Standards for representing protein interactions – Unique IDs from International Protein Index

– Semi-automated curation

– Regularly harvest new data from literature, databases – Build tools to be interoperable


The HVIR Framework

Organize interactions network in biologically meaningful ways

Visualize the network for interactive exploration

Make biological inferences, guide further expts.

Initially create this tool for the Human T-cell Lukemia virus (HTLV-1), its protein, Tax


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Four Objectives of HVIR

• Tools for creating and sharing protein interaction data

• Tools for processing and organizing interaction networks

• Tools for validating interactions

• Tools for evaluating effectiveness and

scalability of the tools above


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Four Objectives of HVIR

• Creating and sharing interactions: literature

mining, standards for representing interactions data, protocols for harvesting data from multiple databases (Open Architecture Initiative)

• Processing interactome networks: clustering using multiple criteria, visualization tools for exploring networks

• Validating content: assign confidence values

using probabilistic models, curate ones with low confidence

• Evaluate effectiveness: focus groups of users evaluate how HVIR guides experimentation


Identifying proteins in Tax complex (Durkin, Semmes)

S-Tax-G FP

kDa 250160 105 75 50





PR04-231 (DNA-PK)

PR04-189 PR04-191 PR04-192 PR04-193


PR04-195 PR04-196

kDa 160 105 75 50


30 250







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Tax co-localizes with activated DNA-PK (Durkin, Semmes)

STaxGFP Nuclear stain


p-T2609 merge


Summary of Work

Designed HVIR to provide virologists with data on protein interaction networks

Four major sets of tools: creating interaction data, processing it, validating it, and

evaluating effectiveness.

Built a prototype for the HTLV-1 virus in collaboration with virologists and

demonstrated it to them.

The Tax interactome now known to include 82 proteins vs. 8 when we began.

Seeking funding to build and extend HVIR.


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Future work

• Detailed study of the Tax interactome to

generate predictions and validate utility of HVIR.

• Build HVIR and make it available for use by biologists.

• Employ a second virus, cytomegalovirus (CMV), with a larger set of proteins to study scalability (Julie Kerry, EVMS).

• Promote standards for data representation and interoperable protocols for data harvesting.


HVIR Input form


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Tax interactors


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Second neighbors of Tax


Local network of selected protein


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FR Layout, selected proteins


A subnetwork of selected proteins


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A subnetwork of sel. proteins


Incremental Navigation


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Incremental Navigation


Shortest path from Tax


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Zooming in on a subnetwork


Current version of Tax network

N = 82



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