Q (haiku): Can you analyze thyroid hormone gene expression by diagnosis in the Pediatric Brain Tumor Atlas (PBTA, Provisional) cohort? ▶ read_guide { "uri": "cbioportal://clinical-data-guide" } ▶ resolve_and_route { "studyKeywords": [ "pediatric", "brain", "tumor", "PBTA" ] } ◀ result # Clinical Data Query Guide ## Overview Clinical data in cBioPortal is stored at both patient and sample levels. Understanding the distinction is crucial for accurate analysis. ## Data Organization ### Patient-Level vs Sample-Level Data - **Patient-level**: Demographics, overall survival, disease stage (stored once per patient) - **Sample-level**: Sample type, sequencing platform, purity (can have multiple per patient) ### Key Tables - `clinical_patient`: Patient-level clinical attributes - `clinical_sample`: Sample-level clinical attributes - `clinical_data_derived`: Pre-joined view combining both levels - `clinical_attribute_meta`: Metadata about available clinical attributes ## Recommended Approach: Use clinical_data_derived The `clinical_data_derived` table is pre-joined and optimized for most queries: ```sql -- Get clinical data for specific attributes SELECT sample_unique_id, patient_unique_id, attribute_name, attribute_value FROM clinical_data_derived WHERE cancer_study_identifier = 'your_study_id' AND attribute_name IN ('CANCER_TYPE', 'SAMPLE_TYPE', 'TMB_NONSYNONYMOUS'); ``` ## Clinical Attribute Discovery ### Use clinical_attribute_meta for Discovering Available Attributes **Always start here** to see what clinical attributes are available for a specific study: ```sql -- Discover available clinical attributes for a study SELECT attr_id, description, patient_attribute, cancer_study_id FROM clinical_attribute_meta WHERE cancer_study_id = ( SELECT cancer_study_id FROM cancer_study WHERE cancer_study_identifier = 'your_study_id' ) ORDER BY patient_attribute, attr_id; ``` **Key Fields:** - **attr_id**: matches attr_id in clinical_sample/clinical_patient tables - **description**: human-readable description of the attribute - **patient_attribute**: true = patient attribute, false = sample attribute - **cancer_study_id**: links to cancer_study table (filter by study) ## Attribute Semantics and Matching ### Case-Insensitive Matching for Attribute Values Clinical values are free text across studies and may differ only by case. For example, a controlled-looking value such as germline mutation status may appear as `GERMLINE`, `Germline`, or another case variant. When filtering `clinical_data_derived.attribute_value`, use case-insensitive matching unless you have already profiled the exact values in the target study: ```sql -- Correct: case-insensitive clinical value filter SELECT DISTINCT sample_unique_id, patient_unique_id FROM clinical_data_derived WHERE cancer_study_identifier = 'your_study_id' AND attribute_name = 'MUTATION_STATUS' AND upper(attribute_value) = 'GERMLINE'; ``` Do not write `attribute_value = 'GERMLINE'` without first checking all distinct values for that attribute in the study. ### Query the Requested Attribute, Not a Proxy Do not infer one clinical attribute from a related subtype or marker. Query the actual requested attribute when it … (17073 more chars) ◀ result {"success":false,"error":"No matching studies found","details":{"searchTerms":["pediatric","brain","tumor","PBTA"]}} ▶ resolve_and_route { "studyKeywords": [ "pediatric", "brain" ] } ◀ result {"success":true,"message":"Found 1 study. Use the metadata to call the appropriate navigation tool(s).","data":{"totalCount":1,"studiesWithMetadata":[{"studyId":"brain_cptac_2020","name":"Pediatric Brain Cancer (CPTAC/CHOP, Cell 2020)","sampleCount":218,"studyViewUrl":"https://www.cbioportal.org/study?id=brain_cptac_2020","metadata":{"clinicalAttributeIds":["AGE","AGE_AT_CHEMOTHERAPY_START","AGE_AT_CHEMOTHERAPY_STOP","AGE_AT_INITIAL_DIAGNOSIS","AGE_AT_LAST_KNOWN_CLINICAL_STATUS","AGE_AT_RADIATION_START","AGE_AT_RADIATION_STOP","AGE_AT_SPECIMEN_DIAGNOSIS","AGE_CLASS","BRAF_RELA_STATUS","BRAF_STATUS","BRAF_STATUS2","CANCER_PREDISPOSITIONS","CANCER_TYPE","CANCER_TYPE_DETAILED","CHEMOTHERAPY","CHEMOTHERAPY_AGENTS","CHEMOTHERAPY_TYPE","CLINICAL_STATUS_AT_COLLECTION_EVENT","COMPLETED_RADIATION_DOSE","COMPLETED_TOTAL_RADIATION_DOSE","CTNNB1_STATUS","DFS_MONTHS","DFS_STATUS","EPENDYMOMA_RELA_STATUS","ETHNICITY","EXTENT_OF_TUMOR_RESECTION","EXTERNAL_PATIENT_ID","FORMULATION","H3F3A_CTNNB1_STATUS","HGG_H3F3A_STATUS","INITIAL_CNS_TUMOR_DIAGNOSIS_RELATED_TO_OS","INITIAL_DIAGNOSIS_TYPE","LGG_BRAF_STATUS","MEDICAL_CONDITIONS","MULTIPLE_CANCER_PREDISPOSITIONS","MULTIPLE_MEDICAL_CONDITIONS","MULTIPLE_TUMOR_LOCATIONS","MUTATION_COUNT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","PROTOCOL_AND_TREATMENT_ARM","RACE","RADIATION","RADIATION_SITE","RADIATION_TYPE","SAMPLE_ANNOTATION","SAMPLE_COUNT","SAMPLE_ORIGIN","SEX","SURGERY","TIMING_OTHER_NOTES","TREATMENT","TREATMENT_CHANGED","TREATMENT_STATUS","TUMOR_LOCATION_CONDENSED","TUMOR_TISSUE_SITE","TUMOR_TYPE","UPDATED_GRADE"],"molecularProfileIds":["brain_cptac_2020_cna","brain_cptac_2020_log2CNA","brain_cptac_2020_mutations","brain_cptac_2020_protein_quantification","brain_cptac_2020_protein_quantification_zscores","brain_cptac_2020_rna_seq_v2_mrna","brain_cptac_2020_rna_seq_v2_mrna_median_Zscores"],"genericAssayProfiles":["brain_cptac_2020_phosphoprotein"],"heatmapProfileIds":["brain_cptac_2020_protein_quantification_zscores","brain_cptac_2020_rna_seq_v2_mrna_median_Zscores"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations","mrna","protein","generic_assay_phoshoprotein_expression"]}}]}} ▶ list_studies { "search": "PBTA", "limit": "10" } ✗ error Error: No such tool available: mcp__navigator__list_studies ▶ clickhouse_list_tables {} ✗ error Error: No such tool available: mcp__clickhouse_list_tables ▶ clickhouse_run_select_query { "query": "SELECT cancer_study_identifier, name, type_of_cancer_id FROM cancer_study WHERE LOWER(name) LIKE '%pbta%' OR LOWER(cancer_study_identifier) LIKE '%pbta%' ORDER BY name LIMIT 10;", "max_rows": 20 } ◀ result {"rows":[]} ▶ clickhouse_run_select_query { "query": "SELECT cancer_study_identifier, name, type_of_cancer_id, sample_count FROM cancer_study WHERE LOWER(name) LIKE '%pediatric%' OR LOWER(name) LIKE '%brain%' OR LOWER(cancer_study_identifier) LIKE '%brain%' ORDER BY sample_count DESC LIMIT 20;", "max_rows": 30 } ◀ result {"rows":[{"cancer_study_identifier":"all_phase2_target_2018_pub","name":"Pediatric Acute Lymphoid Leukemia - Phase II (TARGET, 2018)","type_of_cancer_id":"bll","sample_count":1978},{"cancer_study_identifier":"nbl_target_2018_pub","name":"Pediatric Neuroblastoma (TARGET, 2018)","type_of_cancer_id":"nbl","sample_count":1089},{"cancer_study_identifier":"aml_target_2018_pub","name":"Pediatric Acute Myeloid Leukemia (TARGET, 2018)","type_of_cancer_id":"aml","sample_count":1025},{"cancer_study_identifier":"pediatric_dkfz_2017","name":"Pediatric Pan-Cancer (DKFZ, Nature 2017)","type_of_cancer_id":"mixed","sample_count":961},{"cancer_study_identifier":"aml_stjude_2024","name":"Pediatric Acute Myeloid Leukemia (St. Jude, Nat Genet 2024)","type_of_cancer_id":"aml","sample_count":887},{"cancer_study_identifier":"pancan_mappyacts_2022","name":"Pediatric European MAPPYACTS Trial (Gustave Roussy, Cancer Discov 2022)","type_of_cancer_id":"mixed","sample_count":786},{"cancer_study_identifier":"wt_target_2018_pub","name":"Pediatric Wilms' Tumor (TARGET, 2018)","type_of_cancer_id":"wt","sample_count":657},{"cancer_study_identifier":"lgg_tcga","name":"Brain Lower Grade Glioma (TCGA, Firehose Legacy)","type_of_cancer_id":"difg","sample_count":530},{"cancer_study_identifier":"lgg_tcga_pan_can_atlas_2018","name":"Brain Lower Grade Glioma (TCGA, PanCancer Atlas)","type_of_cancer_id":"difg","sample_count":514},{"cancer_study_identifier":"bm_nsclc_mskcc_2023","name":"Non-Small Cell Lung Cancer Brain Metastasis (MSK, Nat Commun 2023)","type_of_cancer_id":"nsclc","sample_count":322},{"cancer_study_identifier":"brain_cptac_gdc","name":"CNS/Brain Cancer (CPTAC GDC, 2025)","type_of_cancer_id":"brain","sample_count":314},{"cancer_study_identifier":"pptc_2019","name":"Pediatric Preclinical Testing Consortium (CHOP, Cell Rep 2019)","type_of_cancer_id":"mixed","sample_count":261},{"cancer_study_identifier":"nbl_msk_2023","name":"Pediatric Neuroblastoma (MSK, Nat Genet 2023)","type_of_cancer_id":"nbl","sample_count":223},{"cancer_study_identifier":"brain_cptac_2020","name":"Pediatric Brain Cancer (CPTAC/CHOP, Cell 2020)","type_of_cancer_id":"brain","sample_count":218},{"cancer_study_identifier":"prostate_pcbm_swiss_2019","name":"Prostate Cancer Brain Metastases (Bern, Nat Commun. 2022)","type_of_cancer_id":"prostate","sample_count":168},{"cancer_study_identifier":"pancan_pdx_uthsa_2023","name":"Pediatric solid tumor PDXs (UTHSA, Nat Commun 2023)","type_of_cancer_id":"mixed","sample_count":136},{"cancer_study_identifier":"mixed_kunga_msk_2022","name":"Pediatric Pancan Tumors (MSK,Nat Commun. 2022)","type_of_cancer_id":"mixed","sample_count":135},{"cancer_study_identifier":"es_dfarber_broad_2014","name":"Pediatric Ewing Sarcoma (DFCI, Cancer Discov 2014)","type_of_cancer_id":"es","sample_count":107},{"cancer_study_identifier":"gbm_mayo_pdx_sarkaria_2019","name":"Brain Tumor PDXs (Mayo Clinic, Clin Cancer Res 2020)","type_of_cancer_id":"difg","sample_count":106},{"cancer_study_ident … (136 more chars) ▶ clickhouse_run_select_query { "query": "-- Check available cancer types/diagnoses in the pediatric brain cancer study SELECT DISTINCT attribute_value as diagnosis FROM clinical_data_derived WHERE cancer_study_identifier = 'brain_cptac_2020' AND attribute_name IN ('CANCER_TYPE_DETAILED', 'CANCER_TYPE') ORDER BY diagnosis;", "max_rows": 50 } ◀ result {"rows":[{"diagnosis":"Atypical Teratoid/Rhabdoid Tumor"},{"diagnosis":"CNS Cancer"},{"diagnosis":"Craniopharyngioma, Adamantinomatous Type"},{"diagnosis":"Embryonal Tumor"},{"diagnosis":"Ependymomal Tumor"},{"diagnosis":"Ganglioglioma"},{"diagnosis":"Glioma"},{"diagnosis":"High-grade glioma/astrocytoma"},{"diagnosis":"Low-grade glioma/astrocytoma"},{"diagnosis":"Medulloblastoma"},{"diagnosis":"Pediatric High Grade Gliomas"},{"diagnosis":"Pediatric Low Grade Gliomas"},{"diagnosis":"Sellar Tumor"}]} ▶ clickhouse_run_select_query { "query": "-- Check what thyroid hormone related genes have expression data SELECT DISTINCT hugo_gene_symbol FROM genomic_event_derived WHERE cancer_study_identifier = 'brain_cptac_2020' AND molecular_profile_id LIKE '%rna%' AND hugo_gene_symbol IN ('TSHR', 'TPO', 'TG', 'TPOX', 'TRH', 'TRHR', 'TSH') ORDER BY hugo_gene_symbol;", "max_rows": 20 } ◀ result {"error_message":"Query execution failed: HTTPDriver for https://dl96orhu96.us-east-1.aws.clickhouse.cloud:8443 received ClickHouse error code 47\n Code: 47. DB::Exception: Unknown expression or function identifier `molecular_profile_id` in scope SELECT DISTINCT hugo_gene_symbol FROM genomic_event_derived WHERE (cancer_study_identifier = 'brain_cptac_2020') AND (molecular_profile_id LIKE '%rna%') AND (hugo_gene_symbol IN ('TSHR', 'TPO', 'TG', 'TPOX', 'TRH', 'TRHR', 'TSH')) ORDER BY hugo_gene_symbol ASC. (UNKNOWN_IDENTIFIER) (version 26.4.1.2359 (official build))\n"} ▶ clickhouse_list_table_columns { "table": "genomic_event_derived" } ◀ result {"columns":[{"name":"sample_unique_id","type":"String"},{"name":"hugo_gene_symbol","type":"String","comment":"HUGO gene symbol (e.g., TP53, KRAS, BRAF). Use for gene-specific queries."},{"name":"entrez_gene_id","type":"Int32"},{"name":"gene_panel_stable_id","type":"LowCardinality(String)"},{"name":"cancer_study_identifier","type":"LowCardinality(String)"},{"name":"genetic_profile_stable_id","type":"LowCardinality(String)"},{"name":"variant_type","type":"LowCardinality(String)","comment":"Type of genomic event: \"mutation\" for SNVs/indels, \"cna\" for copy number alterations, \"structural_variant\" for SVs. Always filter by this."},{"name":"mutation_variant","type":"String","comment":"Protein change notation (e.g., p.V600E, p.R175H). Use for specific variant queries. \"NA\" for non-mutation events."},{"name":"mutation_type","type":"LowCardinality(String)"},{"name":"mutation_status","type":"LowCardinality(String)","comment":"For mutations: Somatic, Germline, UNKNOWN, or UNCALLED. Filter mutation_status != \"UNCALLED\" to exclude uncertain calls. Include all other statuses."},{"name":"driver_filter","type":"LowCardinality(String)"},{"name":"driver_filter_annotation","type":"String"},{"name":"driver_tiers_filter","type":"LowCardinality(String)"},{"name":"driver_tiers_filter_annotation","type":"String"},{"name":"cna_alteration","type":"Nullable(Int8)","comment":"Copy number alteration: only 2 = amplification (AMP) and -2 = deep deletion (HOMDEL) are stored. Shallow deletion (-1), diploid (0) and gain (1) are not in this table; query genetic_alteration_derived WHERE profile_type = 'gistic' (alteration_value is a String, e.g. '-1'). NULL for non-CNA events."},{"name":"cna_cytoband","type":"String"},{"name":"sv_event_info","type":"String"},{"name":"patient_unique_id","type":"String"},{"name":"off_panel","type":"Bool","comment":"Boolean: 1 = mutation outside gene panel coverage (off-panel), 0 = within panel (on-panel). Filter off_panel = 0 for reliable frequency calculations."}]} ▶ clickhouse_run_select_query { "query": "-- Check what thyroid hormone related genes have expression data SELECT DISTINCT hugo_gene_symbol, genetic_profile_stable_id FROM genomic_event_derived WHERE cancer_study_identifier = 'brain_cptac_2020' AND genetic_profile_stable_id LIKE '%rna%' AND hugo_gene_symbol IN ('TSHR', 'TPO', 'TG', 'TPOX', 'TRH', 'TRHR', 'TSH', 'TSHB', 'CGA') ORDER BY hugo_gene_symbol;", "max_rows": 20 } ◀ result {"rows":[]} ▶ clickhouse_run_select_query { "query": "-- Check what molecular profiles are available for expression data SELECT DISTINCT genetic_profile_stable_id FROM genomic_event_derived WHERE cancer_study_identifier = 'brain_cptac_2020' ORDER BY genetic_profile_stable_id;", "max_rows": 30 } ◀ result {"rows":[{"genetic_profile_stable_id":"brain_cptac_2020_cna"},{"genetic_profile_stable_id":"brain_cptac_2020_mutations"}]} ▶ clickhouse_list_table_columns { "table": "genetic_alteration_derived" } ◀ result {"columns":[{"name":"sample_unique_id","type":"String"},{"name":"cancer_study_identifier","type":"LowCardinality(String)"},{"name":"hugo_gene_symbol","type":"String"},{"name":"profile_type","type":"LowCardinality(String)"},{"name":"alteration_value","type":"Nullable(String)"}]} ▶ clickhouse_run_select_query { "query": "-- Check available expression profile types and sample genes SELECT DISTINCT profile_type FROM genetic_alteration_derived WHERE cancer_study_identifier = 'brain_cptac_2020' ORDER BY profile_type;", "max_rows": 20 } ◀ result {"rows":[{"profile_type":"cna"},{"profile_type":"log2CNA"},{"profile_type":"protein_quantification"},{"profile_type":"protein_quantification_zscores"},{"profile_type":"rna_seq_v2_mrna"},{"profile_type":"rna_seq_v2_mrna_median_Zscores"}]} ▶ clickhouse_run_select_query { "query": "-- Check what thyroid hormone genes have expression data SELECT DISTINCT hugo_gene_symbol FROM genetic_alteration_derived WHERE cancer_study_identifier = 'brain_cptac_2020' AND profile_type = 'rna_seq_v2_mrna' AND hugo_gene_symbol IN ('TSHR', 'TPO', 'TG', 'TPOX', 'TRH', 'TRHR', 'TSH', 'TSHB', 'CGA', 'FSHB', 'LHB') ORDER BY hugo_gene_symbol;", "max_rows": 20 } ◀ result {"rows":[{"hugo_gene_symbol":"CGA"},{"hugo_gene_symbol":"FSHB"},{"hugo_gene_symbol":"LHB"},{"hugo_gene_symbol":"TG"},{"hugo_gene_symbol":"TPO"},{"hugo_gene_symbol":"TRH"},{"hugo_gene_symbol":"TRHR"},{"hugo_gene_symbol":"TSHB"},{"hugo_gene_symbol":"TSHR"}]} ▶ clickhouse_run_select_query { "query": "-- Thyroid hormone gene expression by diagnosis WITH diagnosis_data AS ( SELECT sample_unique_id, anyIf(attribute_value, attribute_name LIKE '%CANCER_TYPE%') as diagnosis FROM clinical_data_derived WHERE cancer_study_identifier = 'brain_cptac_2020' GROUP BY sample_unique_id ), expr_data AS ( SELECT sample_unique_id, hugo_gene_symbol, toFloat64OrNull(alteration_value) as expression_value FROM genetic_alteration_derived WHERE cancer_study_identifier = 'brain_cptac_2020' AND profile_type = 'rna_seq_v2_mrna' AND hugo_gene_symbol IN ('TSHR', 'TPO', 'TG', 'TRH', 'TRHR', 'TSHB', 'CGA') ) SELECT d.diagnosis, e.hugo_gene_symbol, COUNT(*) as n_samples, ROUND(AVG(e.expression_value), 2) as mean_expression, ROUND(MEDIAN(e.expression_value), 2) as median_expression, ROUND(MIN(e.expression_value), 2) as min_expression, ROUND(MAX(e.expression_value), 2) as max_expression FROM diagnosis_data d JOIN expr_data e ON d.sample_unique_id = e.sample_unique_id WHERE d.diagnosis IS NOT NULL GROUP BY d.diagnosis, e.hugo_gene_symbol ORDER BY d.diagnosis, e.hugo_gene_symbol;", "max_rows": 100 } ◀ result {"error_message":"Query execution failed: HTTPDriver for https://dl96orhu96.us-east-1.aws.clickhouse.cloud:8443 received ClickHouse error code 63\n Code: 63. DB::Exception: Unknown aggregate function MEDIAN. Maybe you meant: ['median','medianDD']. (UNKNOWN_AGGREGATE_FUNCTION) (version 26.4.1.2359 (official build))\n"} ▶ clickhouse_run_select_query { "query": "-- Thyroid hormone gene expression by diagnosis WITH diagnosis_data AS ( SELECT sample_unique_id, anyIf(attribute_value, attribute_name LIKE '%CANCER_TYPE%') as diagnosis FROM clinical_data_derived WHERE cancer_study_identifier = 'brain_cptac_2020' GROUP BY sample_unique_id ), expr_data AS ( SELECT sample_unique_id, hugo_gene_symbol, toFloat64OrNull(alteration_value) as expression_value FROM genetic_alteration_derived WHERE cancer_study_identifier = 'brain_cptac_2020' AND profile_type = 'rna_seq_v2_mrna' AND hugo_gene_symbol IN ('TSHR', 'TPO', 'TG', 'TRH', 'TRHR', 'TSHB', 'CGA') ) SELECT d.diagnosis, e.hugo_gene_symbol, COUNT(*) as n_samples, ROUND(AVG(e.expression_value), 2) as mean_expression, ROUND(quantile(0.5)(e.expression_value), 2) as median_expression, ROUND(MIN(e.expression_value), 2) as min_expression, ROUND(MAX(e.expression_value), 2) as max_expression FROM diagnosis_data d JOIN expr_data e ON d.sample_unique_id = e.sample_unique_id WHERE d.diagnosis IS NOT NULL GROUP BY d.diagnosis, e.hugo_gene_symbol ORDER BY d.diagnosis, e.hugo_gene_symbol;", "max_rows": 100 } ◀ result {"rows":[{"diagnosis":"CNS Cancer","hugo_gene_symbol":"CGA","n_samples":28,"mean_expression":0.13,"median_expression":0.12,"min_expression":-0.14,"max_expression":1.35},{"diagnosis":"CNS Cancer","hugo_gene_symbol":"TG","n_samples":28,"mean_expression":1.28,"median_expression":1.08,"min_expression":0.16,"max_expression":3.14},{"diagnosis":"CNS Cancer","hugo_gene_symbol":"TPO","n_samples":28,"mean_expression":0.12,"median_expression":0.14,"min_expression":-0.1,"max_expression":0.4},{"diagnosis":"CNS Cancer","hugo_gene_symbol":"TRH","n_samples":28,"mean_expression":0.49,"median_expression":0.24,"min_expression":-0.14,"max_expression":2.25},{"diagnosis":"CNS Cancer","hugo_gene_symbol":"TRHR","n_samples":28,"mean_expression":0.14,"median_expression":0.16,"min_expression":-0.09,"max_expression":0.46},{"diagnosis":"CNS Cancer","hugo_gene_symbol":"TSHB","n_samples":28,"mean_expression":0.15,"median_expression":0.14,"min_expression":-0.07,"max_expression":0.78},{"diagnosis":"CNS Cancer","hugo_gene_symbol":"TSHR","n_samples":28,"mean_expression":1.72,"median_expression":1.09,"min_expression":0.07,"max_expression":4.89},{"diagnosis":"Embryonal Tumor","hugo_gene_symbol":"CGA","n_samples":25,"mean_expression":0.09,"median_expression":0.07,"min_expression":-0.27,"max_expression":0.79},{"diagnosis":"Embryonal Tumor","hugo_gene_symbol":"TG","n_samples":25,"mean_expression":0.5,"median_expression":0.38,"min_expression":-0.02,"max_expression":1.68},{"diagnosis":"Embryonal Tumor","hugo_gene_symbol":"TPO","n_samples":25,"mean_expression":0.17,"median_expression":0.16,"min_expression":-0.2,"max_expression":1.07},{"diagnosis":"Embryonal Tumor","hugo_gene_symbol":"TRH","n_samples":25,"mean_expression":1.34,"median_expression":1.07,"min_expression":0.14,"max_expression":4.12},{"diagnosis":"Embryonal Tumor","hugo_gene_symbol":"TRHR","n_samples":25,"mean_expression":0.3,"median_expression":0.23,"min_expression":-0.26,"max_expression":1.06},{"diagnosis":"Embryonal Tumor","hugo_gene_symbol":"TSHB","n_samples":25,"mean_expression":0.12,"median_expression":0.08,"min_expression":-0.27,"max_expression":0.9},{"diagnosis":"Embryonal Tumor","hugo_gene_symbol":"TSHR","n_samples":25,"mean_expression":1.39,"median_expression":0.88,"min_expression":0.16,"max_expression":4.62},{"diagnosis":"Glioma","hugo_gene_symbol":"CGA","n_samples":18,"mean_expression":0.04,"median_expression":0.04,"min_expression":-0.22,"max_expression":0.27},{"diagnosis":"Glioma","hugo_gene_symbol":"TG","n_samples":18,"mean_expression":0.43,"median_expression":0.4,"min_expression":0.16,"max_expression":1.02},{"diagnosis":"Glioma","hugo_gene_symbol":"TPO","n_samples":18,"mean_expression":0.14,"median_expression":0.16,"min_expression":-0.15,"max_expression":0.4},{"diagnosis":"Glioma","hugo_gene_symbol":"TRH","n_samples":18,"mean_expression":1.39,"median_expression":1.17,"min_expression":0.16,"max_expression":3.87},{"diagnosis":"Glioma","hugo_gene_symbol":"TRHR","n_samples":18,"mean_expression":0.45,"median_expressio … (4000 more chars) ▶ clickhouse_run_select_query { "query": "-- Get sample counts by diagnosis WITH diagnosis_data AS ( SELECT sample_unique_id, anyIf(attribute_value, attribute_name LIKE '%CANCER_TYPE%') as diagnosis FROM clinical_data_derived WHERE cancer_study_identifier = 'brain_cptac_2020' GROUP BY sample_unique_id ) SELECT diagnosis, COUNT(*) as n_samples FROM diagnosis_data WHERE diagnosis IS NOT NULL GROUP BY diagnosis ORDER BY n_samples DESC;", "max_rows": 20 } ◀ result {"rows":[{"diagnosis":"Low-grade glioma/astrocytoma","n_samples":93},{"diagnosis":"Embryonal Tumor","n_samples":34},{"diagnosis":"CNS Cancer","n_samples":32},{"diagnosis":"High-grade glioma/astrocytoma","n_samples":25},{"diagnosis":"Glioma","n_samples":18},{"diagnosis":"Sellar Tumor","n_samples":16},{"n_samples":1}]} ▶ navigate_to_results_view { "studyIds": [ "brain_cptac_2020" ], "genes": [ "TSHR", "TSHB", "TG", "TPO", "TRH", "TRHR", "CGA" ], "tab": "plots", "plotsVertSelection": { "selectedGeneOption": "TSHR", "dataType": "mRNA_expression" }, "plotsHorzSelection": { "selectedGeneOption": "TRH", "dataType": "mRNA_expression" }, "oncoprintHeatmapTracks": [ { "molecularProfileId": "brain_cptac_2020_rna_seq_v2_mrna_median_Zscores", "entities": [ "TSHR", "TSHB", "TG", "TPO", "TRH", "TRHR", "CGA" ] } ] } ◀ result {"success":true,"message":"Navigating to https://www.cbioportal.org/results/plots?cancer_study_list=brain_cptac_2020&gene_list=TSHR%0ATSHB%0ATG%0ATPO%0ATRH%0ATRHR%0ACGA&case_set_id=brain_cptac_2020_all&plots_horz_selection=%7B%22selectedGeneOption%22%3A%227200%22%2C%22dataType%22%3A%22mRNA_expression%22%7D&plots_vert_selection=%7B%22selectedGeneOption%22%3A%227253%22%2C%22dataType%22%3A%22mRNA_expression%22%7D&heatmap_track_groups=brain_cptac_2020_rna_seq_v2_mrna_median_Zscores%2CTSHR%2CTSHB%2CTG%2CTPO%2CTRH%2CTRHR%2CCGA","url":"https://www.cbioportal.org/results/plots?cancer_study_list=brain_cptac_2020&gene_list=TSHR%0ATSHB%0ATG%0ATPO%0ATRH%0ATRHR%0ACGA&case_set_id=brain_cptac_2020_all&plots_horz_selection=%7B%22selectedGeneOption%22%3A%227200%22%2C%22dataType%22%3A%22mRNA_expression%22%7D&plots_vert_selection=%7B%22selectedGeneOption%22%3A%227253%22%2C%22dataType%22%3A%22mRNA_expression%22%7D&heatmap_track_groups=brain_cptac_2020_rna_seq_v2_mrna_median_Zscores%2CTSHR%2CTSHB%2CTG%2CTPO%2CTRH%2CTRHR%2CCGA","data":{"studyIds":["brain_cptac_2020"],"studies":[{"studyId":"brain_cptac_2020","name":"Pediatric Brain Cancer (CPTAC/CHOP, Cell 2020)","sampleCount":218}],"genes":["TSHR","TSHB","TG","TPO","TRH","TRHR","CGA"],"caseSetId":"brain_cptac_2020_all","oncoprintHeatmapTracks":[{"molecularProfileId":"brain_cptac_2020_rna_seq_v2_mrna_median_Zscores","entities":["TSHR","TSHB","TG","TPO","TRH","TRHR","CGA"]}],"pageDescription":"Scatter/box plots: TSHR mrna_expression (y-axis) by TRH mrna_expression (x-axis)."}} ═ answer (success) Perfect! Now let me create a summary document with the findings: ## Thyroid Hormone Gene Expression Analysis in Pediatric Brain Tumors **Important Note:** The PBTA (Provisional) cohort is not available in this cBioPortal instance. The analysis below uses the **Pediatric Brain Cancer (CPTAC/CHOP, Cell 2020)** cohort, which includes 218 samples across multiple pediatric CNS tumor types. ### Dataset Overview - **Study:** Pediatric Brain Cancer (CPTAC/CHOP, Cell 2020) — `brain_cptac_2020` - **Total samples analyzed:** 219 samples - **Diagnoses:** 7 categories ranging from low-grade gliomas to embryonal tumors and sellar tumors ### Thyroid Hormone Gene Expression by Diagnosis The analysis examined expression of 7 thyroid hormone-related genes: - **TSH axis:** TSHR (TSH receptor), TSHB (TSH β-subunit), CGA (common α-subunit) - **Thyroid-specific:** TPO (thyroid peroxidase), TG (thyroglobulin) - **TRH axis:** TRH (thyrotropin-releasing hormone), TRHR (TRH receptor) **Key Findings:** | Diagnosis | N Samples | Notable Genes | Observations | |-----------|-----------|---|---| | **Low-grade glioma/astrocytoma** | 93 | **TRH**: median 2.22 (range: -0.12 to 6.88) | Highest TRH expression; lowest TSHR (median 0.31); minimal thyroid-specific gene expression | | **Embryonal Tumor** | 34 | **TSHR**: median 0.88; **TRH**: median 1.07 | Balanced TSH and TRH axis expression; moderate TG (median 0.38) | | **CNS Cancer** | 32 | **TSHR**: median 1.09; **TG**: median 1.08 | Elevated TSHR and TG expression; high TRH variance (mean 0.49) | | **High-grade glioma/astrocytoma** | 25 | **TRH**: median 1.95 (highest); **TSHR**: median 0.32 | Pronounced TRH elevation; reduced TSHB (median -0.09) | | **Glioma** | 18 | **TSHR**: median 0.48; **TRH**: median 1.17 | Mixed glioma group; moderate TRH expression | | **Sellar Tumor** | 16 | **CGA**: median -0.06 (variance high); **TSHB**: median -0.16 | Most variable expression; sellar origin may explain CGA/TSHB variability | | Unclassified | 1 | N/A | — | ### Gene-Specific Insights 1. **TRH (Thyrotropin-Releasing Hormone):** Most consistently elevated across diagnoses, with highest median expression in low-grade and high-grade gliomas (2.22 and 1.95, respectively), suggesting HPA axis involvement in glioma biology. 2. **TSHR (TSH Receptor):** Variable by diagnosis—highest in CNS Cancer (median 1.09) and Embryonal Tumor (median 0.88); notably lower in low-grade gliomas (median 0.31) and high-grade gliomas (median 0.32). 3. **TG (Thyroglobulin):** Expression detected across all diagnoses, moderate to low levels (medians 0.34–1.08), suggesting thyroid marker genes are present but not actively thyroid-differentiating. 4. **TPO (Thyroid Peroxidase):** Minimal expression across all diagnoses (medians -0.04 to 0.16), consistent with non-thyroid CNS tumors. 5. **Sellar Tumors:** Highest CGA variance (range: -0.25 to 8.54), expected given the pituitary/neuroendocrine origin of sellar lesions; heterogeneous TSHB expression. --- ### Interactive Visualization [View thyroid hormone gene expression heatmap and scatter plots](https://www.cbioportal.org/results/plots?cancer_study_list=brain_cptac_2020&gene_list=TSHR%0ATSHB%0ATG%0ATPO%0ATRH%0ATRHR%0ACGA&case_set_id=brain_cptac_2020_all&plots_horz_selection=%7B%22selectedGeneOption%22%3A%227200%22%2C%22dataType%22%3A%22mRNA_expression%22%7D&plots_vert_selection=%7B%22selectedGeneOption%22%3A%227253%22%2C%22dataType%22%3A%22mRNA_expression%22%7D&heatmap_track_groups=brain_cptac_2020_rna_seq_v2_mrna_median_Zscores%2CTSHR%2CTSHB%2CTG%2CTPO%2CTRH%2CTRHR%2CCGA) This link displays a heatmap showing normalized expression (z-scores) across all 218 samples, plus scatter/box plots for direct gene-gene comparisons. --- ### Limitations - PBTA (Provisional) is **not available** in this instance; alternative pediatric brain tumor cohort used - Expression values are log2-transformed RNA-seq (normalized); z-scores available for comparison to cohort mean - Sample sizes vary by diagnosis (93 LGG vs. 16 sellar tumors); small cohorts may have limited statistical power