How to Install

Clone the Repository

git clone https://github.com/collaborativebioinformatics/GeNETwork.git
cd GeNETwork

Get the Data

The knowledge graph is still in development, but the raw data is available on OSF: OSF Project Home

Requirements (Future Graph Development)

Currently, no installation is required beyond accessing the datasets. In the near future, we’ll include:

• Graph database setup (e.g., Amazon Neptune, Neo4j, or RDF tools)
• ETL scripts to ingest compatible data into the graph
• Example queries (Gremlin / SPARQL / Cypher)

Background

Pediatric cancers have historically been underserved in therapeutic development and clinical trials. Unlike adult cancers, they were not previously required to be studied by pharmaceutical companies, leaving most pediatric therapeutic discovery to pediatric researchers themselves.

To address this gap, the FDA created the Pediatric Molecular Target List (PMTL), a list of molecular targets important for studying and developing drugs for pediatric cancers. The RACE for Children Act, USA further strengthened this framework: if a drug company develops a therapy against an actionable mutation or gene in adult cancer, and that gene also appears on the PMTL, the company must either justify excluding pediatric trials or move forward with testing in children.

Building on this foundation, our project focuses on pediatric cancers using harmonized datasets from the Molecular Targets Project (MTP) which integrates genomic data from Kids First, TARGET, and other pediatric cohorts. This work was spearheaded at the Children's Hospital of Philadelphia, which aligned RNA and DNA sequencing data processed by the Kids First Data Resource Center and harmonized through the OpenPedCan suite of tools (Github cited in Pubmed).

Together, these resources provide a robust and unified data foundation to explore pediatric-specific therapeutic opportunities that align with both clinical priorities (PMTL) and regulatory requirements (RACE Act).

Methods

Data Sources

Source	Purpose
Molecular Targets Project	Catalog of Molecular Targets
FDA PMTL	Pediatric Cancer Target List
TCGA	Adult Cancer Somatic Mutations
CIViC	Clinical variant interpretations
OncoDB	Drug-target interactions
MSigDB	Pathway gene sets
HGNC	Gene nomenclature standardization
StringDB	Protein-protein interactions

Flowchart

Knowledge Graph Schema

Data Processing Pipeline

Data Processing

• Downloaded datasets (TSV, JSON)
• Standardized Schemas for each dataset from different sources using gene_name as primary key
• Load to Open Science Framework (OSF)

Knowledge Graph Construction

• Define Node types
• Define relationships (edges)
• Define properties
• Load data on AWS Neptune

Analysis & Querying

• Use Cypher
• • Cross-age repurposing via shared variants
  • Pathway-level repurposing
  • TCGA-specific insights
  • Drug-Repurposing Opportunities
  • Variants in Both Adult and Pediatric Cancers
  • Co-mutation Analysis
  • Therapeutic Gaps
  • Paths from Variant to Drug

Visualization/Outputs

• Network/ Graph Visualizations
• Downloadable Summary Tables