Intro

Biological networks play a fundamental role in today’s systems-based biology, pharmacology, and toxicolog as they create the link between experimental measurements and a priori knowledge.
Network models consist of qualitative causal relationships between biological entities to represent current scientific knowledg.
They are represented in a human-readable and computable language (BEL) used for representing scientific knowledge in a standard way.
The purpose of the Network Verification Challenges is to engage the scientific community to review, challenge as well as make corrections to the conventional wisdom on various molecular mechanisms.

Background
Challenge detail
Participants
Scoring and ranking
sbv IMPROVER events
Media library
Testimonials

BACKGROUND

Biological expression language (BEL)

 

BEL represents scientific knowledge in human readable and computable format as semantic triples (subject, a predicate, and an object).

 

BEL

Xenobiotic metabolism

Xenobiotic metabolism is activated in response to any chemical substance foreign to the body (e.g., toxic compounds, drugs). Very briefly, enzymes involved in this process convert xenobiotics into hydrophilic derivatives that can be eliminated through excretion into the aqueous compartments of the tissues.

Philip Morris International (PMI) has invested a great effort to develop computational methodology to predict early toxicity using Causal Biological Network Models and high throughput molecular data.

Previously developed network models were scripted in BEL and focused on pulmonary and vascular biology. Since the liver is the main site of xenobiotic metabolism in mammals, we have developed a new suite of network models that represent biotransformation and chemical elimination involved in Phase I, Phase II and Phase III xenobiotic metabolism in the liver.

Applications of network models

In addition to providing a valuable repository for literature knowledge of various biological processes, the causal biological network models can be scored with transcriptomics data, which opens a myriad of opportunities to gain genome-wide insights in defined biological context.

The network models can also be used to generate hypotheses and to identify the components responsible for biological phenomena in an unbiased way. This allows researchers to design targeted experiments to verify further and extend the insights obtained using high-throughput approaches.

Compound-specific network signatures provide mechanistic insights into the similarities and differences by which toxicants impact biological systems, allowing the toxicity prediction of uncharacterized compounds.

Finally, network model scoring can facilitate biomarker discovery, predict adverse drug reactions, and support personalized medicine by mechanistically explaining patients’ differences concerning disease prevention, diagnosis, and therapy outcome.

application_network_models

The leaderboard: gamifying principle to encourage participation

Leaderboard

Gamification principles are widely used to support user engagement and enhance positive patterns in service use. It results in increased motivation and engagement in the learning and enjoyment over the tasks.

 

The challenge

Components of a network verification challenge

The organization of a network verification challenge entails:

  • A number of network models available for review;
  • A web platform to visualize, verify, and collaboratively refine the networks: ( the Bionet platform;
  • A leaderboard to keep track of the competition;
  • A conference/jamboree to meet and collaborate around the networks.

The overall process is illustrated below:

NVC_process

Challenge overview

NVC3

NVC3: Liver xenobiotic metabolism networks

NVC2

NVC2: Lung biology

A summary of the challenge outcome is given in the below picture.

summary_outcome_NVC2
NVC1

NVC1: Lung biology

A summary of the challenge outcome is given in the below picture.

summary_outcome_NVC1

Rules and awards

Description

Challenge participants

sbv participation map

Leaderboard: best performers

Best performers

NVC3

NVC3: Liver xenobiotic metabolism networks

The top 3 best performers in the NVC3 are:

  • Aravind Tallam from the Charité Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany;
  • Sphoorthy Pravas University of Bonn, Germany, Germany; and
  • Trinidad Martin from the SIB (Swiss Institute of Bioinformatics), Geneva, Switzerland.
NVC2

NVC2: Lung biology

The best performers were announced at the sbv IMPROVER Jamboree 2015 in Barcelona, Spain and the identity of the Best Performers was published in Nature (Volume 523 Number 7562, 30 July 2015, page 495).

Best_performers_announce-NVC2
NVC1

NVC1: Lung biology

The best performers were announced at the sbv IMPROVER Jamboree 2014 in Montreux, Switzerland and the identity of the best performers was published in Nature (Volume 509 Number 7499, 8 May 2014, page 127).

NVC2_announcement_BP

Challenge symposia

In order to congratulate the best performers and share the learnings of the challenges, different symposia have been organized, alongside larger conferences, or as standalone events.

Network Verification Challenge 3: Liver xenobiotic metabolism networks

The sbv IMPROVER NVC3 workshop 2018 was successfully conducted the PMI R&D facilities in Neuchatel, Switzerland on June 27th 2018. The symposium included:

  • The results and presentation of awards for the Network Verification Challenge III
  • Keynote presentations on biological networks
  • Discussions on the 3D liver microtissues study design

Network Verification Challenge 2: Lung biology

The sbv IMPROVER Jamboree 2015 was successfully conducted at the Rey Juan Carlos I Hotel, Barcelona, Spain, on 15 - 18 June 2015. The event included lectures, biological network review sessions (jamboree), and social events and networking.

On Wednesday 17th June 2015, the conference was open to the scientific community.

The meeting had two main objectives:

  • Review and agree on the existence of a selection of edges and evidences that were disputed by challenge participants during the online verification process.
  • Gather lessons learned from the Network Verification Challenge.

The Jamboree brought together:

  • The “best performing” participants in the Network Verification Challenge, as determined by reputation points;
  • Subject matter experts;
  • The team of scientists who generated the initial networks models.

Network Verification Challenge 1: Lung biology

The sbv IMPROVER Jamboree 2014 was successfully conducted at Le Montreux Palace, Montreux, Switzerland, on 18 - 20 March 2014. The event included lectures, biological network review sessions (jamboree), and social events and networking.

Media library

Scientific publications

The challenge in the news

Drug Discovery NewsSep 2016Crowdsourcing lung biologyINTERVALS_Icons-wwwINTERVALS_Icons-pdf
Drug Discovery TodayAug 2016Philip Morris International, IBM Launch Industry-Focused Systems Biology Verification ChallengeINTERVALS_Icons-wwwINTERVALS_Icons-pdf
American LaboratoryAug 2016Community-Verified Biological Network Models Show Promise for Toxicology, Drug Discovery INTERVALS_Icons-pdf
Libertas AcademicaAug 2016Public Science Insights: Community verified biological network modelsINTERVALS_Icons-wwwINTERVALS_Icons-pdf
News MedicalJul 2016Novel community-produced biological network models hold potential in drug discovery and toxicologyINTERVALS_Icons-wwwINTERVALS_Icons-pdf
Asia Pacific Biotech NewsNov 2015A New Look into Toxicology Risk Assessment and Environmental SafetyINTERVALS_Icons-wwwINTERVALS_Icons-pdf
BioSpectrum AsiaJul 2015Network Verification Challenge gains momentumINTERVALS_Icons-wwwINTERVALS_Icons-pdf
American LaboratoryNov 2014Success of the Third sbv IMPROVER Network Verification ChallengeINTERVALS_Icons-wwwINTERVALS_Icons-pdf
Asia Pacific BiotechOct 2014Network Verification Challenge generates COPD network models INTERVALS_Icons-wwwINTERVALS_Icons-pdf
BioSpectrum AsiaAug 2014Hope for COPD: Network Verification ChallengeINTERVALS_Icons-wwwINTERVALS_Icons-pdf
Science 2.0Feb 2014Systems Biology Post-Docs May Have A New Best Friend In...Philip Morris?INTERVALS_Icons-wwwINTERVALS_Icons-pdf
Asia BiotechDec 2013Challenged TO ImproveINTERVALS_Icons-wwwINTERVALS_Icons-pdf
Science ReporterDec 2013Network Verification Challenge open for Scientists INTERVALS_Icons-pdf
Drug Discovery NewsNov 2013All together now...INTERVALS_Icons-wwwINTERVALS_Icons-pdf
American LaboratoryOct 2013Network Verification Challenge opens a new chapter for sbv IMPROVERINTERVALS_Icons-wwwINTERVALS_Icons-pdf
BioSpectrum AsiaOct 2013Network verification challenge to map bio networksINTERVALS_Icons-wwwINTERVALS_Icons-pdf
GenomeWebOct 2013Philips Morris International and IBM Launch Third 'Improver' ChallengeINTERVALS_Icons-wwwINTERVALS_Icons-pdf
PharmaManufacturingOct 2013The Scientific Data Crowdsourcing ChallengeINTERVALS_Icons-wwwINTERVALS_Icons-pdf
BioITWorldOct 2013Network Verification Challenge Opens to AllINTERVALS_Icons-wwwINTERVALS_Icons-pdf

Tutorials

Webinars

Flyers and posters

Testimonials

What they say about the challenge