TCGA RNA-seq V2 Level3 data were downloaded from TCGA Genomic Data Commons Data Portal (https://gdc-portal.nci.nih.gov), consisting of 11,303 samples in 34 cancer projects (33 cancer types). Nine cancer types that do not have corresponding non-tumour samples were filtered out, and the analysis was focused on tumour versus non-tumour comparison. 24 cancer types were used in this meta-analysis: BLCA, BRCA, CESC, CHOL, COAD, ESCA, GBM, HNSC, KICH, KIRC, KIRP, LIHC, LUAD, LUSC, PAAD, PCPG, PRAD, READ, SARC, SKCM, STAD, THCA, THYM, UCEC (https://gdc-portal.nci.nih.gov). The nine filtered cancer types were ACC, DLBC, LAML, LGG, MESO, OV, TGCT, UCS and UVM. To extract expression values from TCGA RNA-seq data, we used genomic coordinates to retrieve UCSC Transcript IDs that correspond to the identifiers in TCGA RNA-seq V2 Level3 data (isoform level). The GAF (General Annotation Format) file was used to map the coordinate to UCSC Transcript ID, and it was downloaded form https://tcga-data.nci.nih.gov/docs/GAF/GAF.hg19.June2011.bundle/outputs/TCGA.hg19.June2011.gaf. This file contains genomic annotations shared by all TCGA projects. More details of the GAF file format can be found at https://tcga-data.nci.nih.gov/docs/GAF/GAF3.0/GAF_v3_file_description.docx. We filtered out any coding exons overlapping UCSC Transcript IDs to eliminate expression value of coding genes and evaluate lncRNA expression.We could find the expression values of 443 pcRNAs and 203 tapRNAs in TCGA data, as many of non-coding regions are not yet fully annotated in the TCGA RNA-seq V2 Level3 data. The expression value of pcRNAs and tapRNAs were extracted and clustered by un-supervised Pearson correlation method (Supplementary Figure 18A). The expression values of tapRNA-associated coding genes were also extracted and used to generate the heat-map (Supplementary Figure 18B), which shows the similar pattern of expression with tapRNAs across the cancer types.To show that tapRNAs and associated coding genes have similar expression profiles in cancers we generated a Spearman's Rank-Order Correlation heatmap (Figure 6A) between tapRNAs and their associated coding genes based on the TCGA RNA-seq data. We used the MatLab function corr to calculate the Spearman's rho. This function takes two matrices X (197-by-8,850 expression profiling matrix of tapRNA) and Y (197-by-8,850 expression profiling matrix of tapRNA-assocated coding gene) and returns an 8,850-by-8,850 matrix containing the pairwise correlation coefficient between each pair of 8,850 columns (TCGA cancer samples in Supplementary Figure 18A and B). Thus, the rank-order correlation matrix that we computed from the matrices of expression profiling data (Supplementary Figure S18A and B) allowed us to compare the correlation between two column vectors i.e. cancer samples. This function also returns a matrix of p-values for testing the hypothesis of no correlation against the alternative that there is a nonzero correlation. Each element of a matrix of p-values is the p value for the corresponding element of Spearman's rho. The p-values for Spearman's rho are calculated using large-sample approximations. To check significance level of correlation between tapRNA and its associated coding gene, the diagonal of the p-value matrix was extracted and used. The median is 1.31x10-11 and the mean is 1.03x10-4 with standard deviation 0.0029.To identify cancer-specific tapRNAs, we considered not only the global expression pattern of a given tapRNA in each cancer type, but also expression pattern of specific sub-group that is significantly distinct, to take into account cancer sample heterogeneity. Thus, two conditions were applied: (1) average expression level of a tapRNA in a given cancer type is in top 10% or bottom 10% and (2) a tapRNA has at least 10% of samples in a given cancer type that are significantly up-regulated (Z-score > 2) or down-regulated (Z-score < -2).

The following datasets were created for Project Cognoma:expression-matrix.tsv.bz2 is a sample × gene matrix indicating a gene's expression level for a given sample. This dataset will be the feature/x/predictor for Project Cognoma.mutation-matrix.tsv.bz2 is a sample × gene matrix indicating whether a gene is mutated for a given sample. Select columns (or unions of several columns) in this dataset will be the status/y/outcome for Project Cognoma.These are preliminary datasets for development use and machine learning. The data was retrieved from the UCSC Xena Browser. All original work in the data is released under CC0. However, the license of TCGA and Xena data is currently unclear.These two datasets are from this GitHub directory linked to below, although they were not tracked due to large file size.

The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data collection is part of a larger effort to build a research community focused on connecting cancer phenotypes to genotypes by providing clinical images matched to subjects from The Cancer Genome Atlas (TCGA). Clinical, genetic, and pathological data resides in the Genomic Data Commons (GDC) Data Portal while the radiological data is stored on The Cancer Imaging Archive (TCIA).

Matched TCGA patient identifiers allow researchers to explore the TCGA/TCIA databases for correlations between tissue genotype, radiological phenotype and patient outcomes. Tissues for TCGA were collected from many sites all over the world in order to reach their accrual targets, usually around 500 specimens per cancer type. For this reason the image data sets are also extremely heterogeneous in terms of scanner modalities, manufacturers and acquisition protocols. In most cases the images were acquired as part of routine care and not as part of a controlled research study or clinical trial.

CIP TCGA Radiology Initiative

Imaging Source Site (ISS) Groups are being populated and governed by participants from institutions that have provided imaging data to the archive for a given cancer type. Modeled after TCGA analysis groups, ISS groups are given the opportunity to publish a marker paper for a given cancer type per the guidelines in the table above. This opportunity will generate increased participation in building these multi-institutional data sets as they become an open community resource. Learn more about the TCGA Breast Phenotype Research Group.

TCGA Cancer Variant and Clinical Data

  Dataset Description

This dataset combines genetic variant information at the protein level with clinical data from The Cancer Genome Atlas (TCGA) project, curated by the International Cancer Genome Consortium (ICGC). It provides a comprehensive view of protein-altering mutations and clinical characteristics across various cancer types.

  Dataset Summary

The dataset includes:

Protein sequence data for both mutated and… See the full description on the dataset page: https://huggingface.co/datasets/seq-to-pheno/TCGA-Cancer-Variant-and-Clinical-Data.

The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) data collection is part of a larger effort to build a research community focused on connecting cancer phenotypes to genotypes by providing clinical images matched to subjects from The Cancer Genome Atlas (TCGA). Clinical, genetic, and pathological data resides in the Genomic Data Commons (GDC) Data Portal while the radiological data is stored on The Cancer Imaging Archive (TCIA).

Matched TCGA patient identifiers allow researchers to explore the TCGA/TCIA databases for correlations between tissue genotype, radiological phenotype and patient outcomes. Tissues for TCGA were collected from many sites all over the world in order to reach their accrual targets, usually around 500 specimens per cancer type. For this reason the image data sets are also extremely heterogeneous in terms of scanner modalities, manufacturers and acquisition protocols. In most cases the images were acquired as part of routine care and not as part of a controlled research study or clinical trial.

CIP TCGA Radiology Initiative

Imaging Source Site (ISS) Groups are being populated and governed by participants from institutions that have provided imaging data to the archive for a given cancer type. Modeled after TCGA analysis groups, ISS groups are given the opportunity to publish a marker paper for a given cancer type per the guidelines in the table above. This opportunity will generate increased participation in building these multi-institutional data sets as they become an open community resource. Learn more about the TCGA Ovarian Phenotype Research Group.

The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) data collection is part of a larger effort to build a research community focused on connecting cancer phenotypes to genotypes by providing clinical images matched to subjects from The Cancer Genome Atlas (TCGA). Clinical, genetic, and pathological data resides in the Genomic Data Commons (GDC) Data Portal while the radiological data is stored on The Cancer Imaging Archive (TCIA).

Matched TCGA patient identifiers allow researchers to explore the TCGA/TCIA databases for correlations between tissue genotype, radiological phenotype and patient outcomes. Tissues for TCGA were collected from many sites all over the world in order to reach their accrual targets, usually around 500 specimens per cancer type. For this reason the image data sets are also extremely heterogeneous in terms of scanner modalities, manufacturers and acquisition protocols. In most cases the images were acquired as part of routine care and not as part of a controlled research study or clinical trial.

CIP TCGA Radiology Initiative

Imaging Source Site (ISS) Groups are being populated and governed by participants from institutions that have provided imaging data to the archive for a given cancer type. Modeled after TCGA analysis groups, ISS groups are given the opportunity to publish a marker paper for a given cancer type per the guidelines in the table above. This opportunity will generate increased participation in building these multi-institutional data sets as they become an open community resource. Learn more about the CIP TCGA Radiology Initiative.

Abstract:

The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. This dataset includes curated survival data from the Pan-cancer Atlas paper titled "An Integrated TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR) to drive high quality survival outcome analytics". The paper highlights four types of carefully curated survival endpoints, and recommends the use of the endpoints of OS, PFI, DFI, and DSS for each TCGA cancer type. The dataset also includes phenotypic information about GBM. The Sample IDs are unique identifiers, which can be paired with the gene expression dataset.

Inspiration:

This dataset was uploaded to UBRITE for GTKB project.

Instruction:

The survival and phenotype data were merged into one file. Empty columns were removed. Columns with the same value for every sample were also removed.

Acknowledgments:

Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8

Liu, Jianfang, Caesar-Johnson, Samantha J. et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell, Volume 173, Issue 2, 400 - 416.e11. https://doi.org/10.1016/j.cell.2018.02.052

The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764

U-BRITE last update: 07/13/2023

Abstract:

The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. This dataset includes curated survival data from the Pan-cancer Atlas paper titled "An Integrated TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR) to drive high quality survival outcome analytics". The paper highlights four types of carefully curated survival endpoints, and recommends the use of the endpoints of OS, PFI, DFI, and DSS for each TCGA cancer type. The dataset also includes phenotypic information about HNSC. The Sample IDs are unique identifiers, which can be paired with the gene expression dataset.

Inspiration:

This dataset was uploaded to UBRITE for GTKB project.

Instruction:

The survival and phenotype data were merged into one file. Empty columns were removed. Columns with the same value for every sample were also removed.

Acknowledgments:

Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8

Liu, Jianfang, Caesar-Johnson, Samantha J. et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell, Volume 173, Issue 2, 400 - 416.e11. https://doi.org/10.1016/j.cell.2018.02.052

The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764

U-BRITE last update: 07/13/2023

Abstract: The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. This dataset includes curated survival data from the Pan-cancer Atlas paper titled "An Integrated TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR) to drive high quality survival outcome analytics". The paper highlights four types of carefully curated survival endpoints, and recommends the use of the endpoints of OS, PFI, DFI, and DSS for each TCGA cancer type. The dataset also includes phenotypic information about LGG. The Sample IDs are unique identifiers, which can be paired with the gene expression dataset. Inspiration: This dataset was uploaded to UBRITE for GTKB project. Instruction: The survival and phenotype data were merged into one file. Empty columns were removed. Columns with the same value for every sample were also removed. Acknowledgments: Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8 Liu, Jianfang, Caesar-Johnson, Samantha J. et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell, Volume 173, Issue 2, 400 - 416.e11. https://doi.org/10.1016/j.cell.2018.02.052 The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764 U-BRITE last update: 07/13/2023 {"references": ["Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8", "Liu, Jianfang, Caesar-Johnson, Samantha J. et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell, Volume 173, Issue 2, 400 - 416.e11.\u00a0https://doi.org/10.1016/j.cell.2018.02.052", "The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113\u20131120 (2013). https://doi.org/10.1038/ng.2764"]} UBRITE location: /data/project/ubrite/gtkb/TCGA/Clinical

Abstract:

The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. This dataset includes curated survival data from the Pan-cancer Atlas paper titled "An Integrated TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR) to drive high quality survival outcome analytics". The paper highlights four types of carefully curated survival endpoints, and recommends the use of the endpoints of OS, PFI, DFI, and DSS for each TCGA cancer type. The dataset also includes phenotypic information about KIRC. The Sample IDs are unique identifiers, which can be paired with the gene expression dataset.

Inspiration:

This dataset was uploaded to UBRITE for GTKB project.

Instruction:

The survival and phenotype data were merged into one file. Empty columns were removed. Columns with the same value for every sample were also removed.

Acknowledgments:

Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8

Liu, Jianfang, Caesar-Johnson, Samantha J. et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell, Volume 173, Issue 2, 400 - 416.e11. https://doi.org/10.1016/j.cell.2018.02.052

The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764

U-BRITE last update: 07/13/2023

Abstract:

The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. This dataset contains information about GBM, an aggressive and highly malignant brain tumor that arises from glial cells, characterized by rapid growth and infiltrative behavior. The gene expression profile was measured experimentally using the Affymetrix HT Human Genome U133a microarray platform by the Broad Institute of MIT and Harvard University cancer genomic characterization center. The Sample IDs serve as unique identifiers for each sample.

Inspiration:

This dataset was uploaded to UBRITE for GTKB project.

Instruction:

The log2(x) normalization was removed, and z-normalization was performed on the dataset using a Python script.

Acknowledgments:

Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8

The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764

U-BRITE last update: 07/13/2023

Abstract:

The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. This dataset contains information about CESC, a type of cancer that affects the cells lining the cervix and can have squamous cell or adenocarcinoma histological subtypes. The gene expression profile was measured experimentally using the Illumina HiSeq 2000 RNA Sequencing platform by the University of North Carolina TCGA genome characterization center. The Sample IDs serve as unique identifiers for each sample.

Inspiration:

This dataset was uploaded to UBRITE for GTKB project.

Instruction:

The log2(x+1) normalization was removed, and z-normalization was performed on the dataset using a Python script.

Acknowledgments:

Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8

The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764

U-BRITE last update: 07/13/2023

Quantitative PCR (qPCR) remains the most widely used technique for gene expression evaluation. Obtaining reliable data using this method requires reference genes (RGs) with stable mRNA level under experimental conditions. This issue is especially crucial in cancer studies because each tumor has a unique molecular portrait. The Cancer Genome Atlas (TCGA) project provides RNA-Seq data for thousands of samples corresponding to dozens of cancers and presents the basis for assessment of the suitability of genes as reference ones for qPCR data normalization. Using TCGA RNA-Seq data and previously developed CrossHub tool, we evaluated mRNA level of 32 traditionally used RGs in 12 cancer types, including those of lung, breast, prostate, kidney, and colon. We developed an 11-component scoring system for the assessment of gene expression stability. Among the 32 genes, PUM1 was one of the most stably expressed in the majority of examined cancers, whereas GAPDH, which is widely used as a RG, showed significant mRNA level alterations in more than a half of cases. For each of 12 cancer types, we suggested a pair of genes that are the most suitable for use as reference ones. These genes are characterized by high expression stability and absence of correlation between their mRNA levels. Next, the scoring system was expanded with several features of a gene: mutation rate, number of transcript isoforms and pseudogenes, participation in cancer-related processes on the basis of Gene Ontology, and mentions in PubMed-indexed articles. All the genes covered by RNA-Seq data in TCGA were analyzed using the expanded scoring system that allowed us to reveal novel promising RGs for each examined cancer type and identify several “universal” pan-cancer RG candidates, including SF3A1, CIAO1, and SFRS4. The choice of RGs is the basis for precise gene expression evaluation by qPCR. Here, we suggested optimal pairs of traditionally used RGs for 12 cancer types and identified novel promising RGs that demonstrate high expression stability and other features of reliable and convenient RGs (high expression level, low mutation rate, non-involvement in cancer-related processes, single transcript isoform, and absence of pseudogenes).

Abstract: The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. This dataset contains information about HNSC, a type of cancer that originates in the squamous cells lining the mucosal surfaces of the head and neck region, including the oral cavity, throat, and larynx. The gene expression profile was measured experimentally using the Illumina HiSeq 2000 RNA Sequencing platform by the University of North Carolina TCGA genome characterization center. The Sample IDs serve as unique identifiers for each sample. Inspiration: This dataset was uploaded to UBRITE for GTKB project. Instruction: The log2(x+1) normalization was removed, and z-normalization was performed on the dataset using a Python script. Acknowledgments: Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8 The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764 U-BRITE last update: 07/13/2023 {"references": ["Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8", "The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113\u20131120 (2013). https://doi.org/10.1038/ng.2764"]} U-BRITE location: /data/project/ubrite/gtkb/TCGA/GeneExp

Following the same steps that we used in the previous course we downloaded the TCGA-BRCA using R and Bioconductor and in particular the TCGABiolinks package. We downloaded transcriptome profiling of gene expression quantification where the experimental strategy is (RNAseq) and the workflow type is HTSeq-FPKM-UQ and only primary solid tumor data of the affymetrix GPL86 profile and clinical data.

TCGA Expedition Modules and associated TCGA Datatypes managed.

Abstract:

The Cancer Genome Atlas (TCGA) was a large-scale collaborative project initiated by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI). It aimed to comprehensively characterize the genomic and molecular landscape of various cancer types. These datasets contain gene expression profiles of bladder urothelial carcinoma (BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), glioblastoma multiforme (GBM), head & neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), and lower grade glioma (LGG).

The gene expression profiles for BLCA, CESC, HNSC, KIRC, and LGG were measured experimentally using the Illumina HiSeq 2000 RNA Sequencing platform by the University of North Carolina TCGA genome characterization center. The gene expression profile of the GBM dataset was measured experimentally using the Affymetrix HT Human Genome U133a microarray platform by the Broad Institute of MIT and Harvard University cancer genomic characterization center.

Inspiration:

This dataset was uploaded to UBRITE for GTKB project.

Instruction:

The log₂(x+1) normalization was removed, and z-normalization was performed on the BLCA, CESC, HNSC, KIRC, and LGG datasets.

The log₂(x) normalization was removed, and z-normalization was performed on the GBM dataset.

Acknowledgments:

Goldman, M.J., Craft, B., Hastie, M. et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol (2020). https://doi.org/10.1038/s41587-020-0546-8.

The Cancer Genome Atlas Research Network., Weinstein, J., Collisson, E. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113–1120 (2013). https://doi.org/10.1038/ng.2764.

U-BRITE last update: 07/13/2023

The Cancer Genome Atlas (TCGA) projects have advanced our understanding of the driver mutations, genetic backgrounds, and key pathways activated across cancer types. Analysis of TCGA datasets have mostly focused on somatic mutations and translocations, with less emphasis placed on gene amplifications. Here we describe a bioinformatics screening strategy to identify putative cancer driver genes amplified across TCGA datasets. We carried out GISTIC2 analysis of TCGA datasets spanning 14 cancer subtypes and identified 461 genes that were amplified in two or more datasets. The list was narrowed to 73 cancer-associated genes with potential “druggable” properties. The majority of the genes were localized to 14 amplicons spread across the genome. To identify potential cancer driver genes, we analyzed gene copy number and mRNA expression data from individual patient samples and identified 40 putative cancer driver genes linked to diverse oncogenic processes. Oncogenic activity was further validated by siRNA/shRNA knockdown and by referencing the Project Achilles datasets. The amplified genes represented a number of gene families, including epigenetic regulators, cell cycle-associated genes, DNA damage response/repair genes, metabolic regulators, and genes linked to the Wnt, Notch, Hedgehog, JAK/STAT, NF-KB and MAPK signaling pathways. Among the 40 putative driver genes were known driver genes, such as EGFR, ERBB2 and PIK3CA. Wild-type KRAS was amplified in several cancer types, and KRAS-amplified cancer cell lines were most sensitive to KRAS shRNA, suggesting that KRAS amplification was an independent oncogenic event. A number of MAP kinase adapters were co-amplified with their receptor tyrosine kinases, such as the FGFR adapter FRS2 and the EGFR family adapter GRB7. The ubiquitin-like ligase DCUN1D1 and the histone methyltransferase NSD3 were also identified as novel putative cancer driver genes. We discuss the patient tailoring implications for existing cancer drug targets and we further discuss potential novel opportunities for drug discovery efforts.

Dataset Card for TCGA-PAAD Clinical Data

  Dataset Summary

The TCGA-PAAD (The Cancer Genome Atlas - Pancreatic Adenocarcinoma) clinical dataset contains clinical data related to pancreatic adenocarcinoma patients. This dataset is part of the broader TCGA project, aimed at providing comprehensive genomic and clinical data for various types of cancer. The clinical data includes information such as patient demographics, treatment history, survival data, and other clinical… See the full description on the dataset page: https://huggingface.co/datasets/HLMCC/TCGA-PAAD.

The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) data collection is part of a larger effort to build a research community focused on connecting cancer phenotypes to genotypes by providing clinical images matched to subjects from The Cancer Genome Atlas (TCGA). Clinical, genetic, and pathological data resides in the Genomic Data Commons (GDC) Data Portal while the radiological data is stored on The Cancer Imaging Archive (TCIA).

Matched TCGA patient identifiers allow researchers to explore the TCGA/TCIA databases for correlations between tissue genotype, radiological phenotype and patient outcomes. Tissues for TCGA were collected from many sites all over the world in order to reach their accrual targets, usually around 500 specimens per cancer type. For this reason the image data sets are also extremely heterogeneous in terms of scanner modalities, manufacturers and acquisition protocols. In most cases the images were acquired as part of routine care and not as part of a controlled research study or clinical trial.

CIP TCGA Radiology Initiative

Imaging Source Site (ISS) Groups are being populated and governed by participants from institutions that have provided imaging data to the archive for a given cancer type. Modeled after TCGA analysis groups, ISS groups are given the opportunity to publish a marker paper for a given cancer type per the guidelines in the table above. This opportunity will generate increased participation in building these multi-institutional data sets as they become an open community resource. Learn more about the CIP TCGA Radiology Initiative.