PCAT: an integrated portal for genomic and preclinical testing data of pediatric cancer patient-derived xenograft models

Abstract

Although cancer is the leading cause of disease-related mortality in children, the relative rarity of pediatric cancers poses a significant challenge for developing novel therapeutics to further improve prognosis. Patient-derived xenograft (PDX) models, which are usually developed from high-risk tumors, are a useful platform to study molecular driver events, identify biomarkers and prioritize therapeutic agents. Here, we develop PDX for Childhood Cancer Therapeutics (PCAT), a new integrated portal for pediatric cancer PDX models. Distinct from previously reported PDX portals, PCAT is focused on pediatric cancer models and provides intuitive interfaces for querying and data mining. The current release comprises 324 models and their associated clinical and genomic data, including gene expression, mutation and copy number alteration. Importantly, PCAT curates preclinical testing results for 68 models and 79 therapeutic agents manually collected from individual agent testing studies published since 2008. To facilitate comparisons of patterns between patient tumors and PDX models, PCAT curates clinical and molecular data of patient tumors from the TARGET project. In addition, PCAT provides access to gene fusions identified in nearly 1000 TARGET samples. PCAT was built using R-shiny and MySQL. The portal can be accessed at http://pcat.zhenglab.info or http://www.pedtranscriptome.org.

Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics

“…Furthermore, all 964 ECM-related genes were studied for patient OS based on RNAsequencing information of 143 NB patients in cBioPortal (TARGET) under Z = 2 setting and the TARGET-NBL data set in PCAT OS estimation using "auto-calculate" cut-offs (2-method selection) (Supplementary Figure S1A) [22]. The vast majority of the ECM-related genes did not correlate with patient prognoses (p-value > 0.05), hence were not taken forward (Supplementary File S3); approximately 5% were linked to altered patient prognoses.…”

“…The list of 964 ECM-related genes was also subjected to the "KEGG_2019_Human" gene ontology module in PCAT http://pedtranscriptome.org/?multiple_genes_enrich_r (accessed on 10 February 2022) [22] (Supplementary File S2). Briefly, the functional enrichment tool using the "KEGG_2019_Human" option was utilised to query the gene list.…”

Computational drug prediction in hepatoblastoma by integrating pan-cancer transcriptomics with pharmacological response

“…We also assessed DrugSense performance in analyzing transcriptional profiles from a collection of 39 PDX for Childhood Cancer Therapeutics (PCAT) portal, [21] of which 31 from solid tumors and 8 from liquid tumors, whose response to 44 drugs was experimentally measured. Out of these 44 drugs, 23 were present in DrugSense for solid tumors, and 21 for liquid tumors (Supplemental Figure S1H, I, http://links.lww.com/HEP/ I17).…”

Comprehensive characterization of patient-derived xenograft models of pediatric leukemia

“…First, most genomic studies in pediatric PDX models do not include germline DNA samples or patient primary tumor samples to delineate somatic from germline genetic alterations. 21 , 22 , 23 , 24 , 25 Second, the majority of published PDX studies have only DNA and RNA sequencing data and fail to explore the epigenomic landscape of either PDX models or matched primary tumors. 21 , 22 , 23 , 24 , 25 Therefore, a comprehensive multi-omics analysis of PDX models including both germline DNA and epigenomics studies are in an urgent need.…”

“… 21 , 22 , 23 , 24 , 25 Second, the majority of published PDX studies have only DNA and RNA sequencing data and fail to explore the epigenomic landscape of either PDX models or matched primary tumors. 21 , 22 , 23 , 24 , 25 Therefore, a comprehensive multi-omics analysis of PDX models including both germline DNA and epigenomics studies are in an urgent need.…”