Q (sonnet): Do samples with TP53 truncating mutations have significantly lower TP53 mRNA expression compared to wild-type samples?

▶ list_guides
{}

◀ result
{"result":[{"uri":"cbioportal://mutation-frequency-guide","description":"Comprehensive guide for calculating gene mutation frequencies with gene-specific profiling denominators"},{"uri":"cbioportal://clinical-data-guide","description":"Guide for querying clinical data including patient vs sample level considerations"},{"uri":"cbioportal://sample-filtering-guide","description":"Guide for filtering samples and studies in cBioPortal queries"},{"uri":"cbioportal://common-pitfalls","description":"Guide to avoid common mistakes when querying cBioPortal data. If you already know which numbered pitfall applies, fetch just that section via read_guide(\"cbioportal://common-pitfalls#<number>\") (e.g. #16) instead of the full guide"},{"uri":"cbioportal://treatment-guide","description":"Guide for querying treatment/clinical event data including drug agents, timelines, and linking to genomic data"},{"uri":"cbioportal://faq-guide","description":"General cBioPortal FAQ: history, how to cite, data types, reference genome, abbreviations, GISTIC thresholds, API access"},{"uri":"cbioportal://statistical-tests-guide","description":"Statistical test selection guide — decision matrix for choosing Fisher's exact, Wilcoxon, chi-squared, t-test, ANOVA, etc. based on data type and group count"},{"uri":"cbioportal://gene-expression-guide","description":"Gene expression / copy-number / methylation analysis. Covers genetic_alteration_derived, profile_type discovery, and the gene_pair_coexpression view for Spearman correlation between two genes"},{"uri":"cbioportal://external-resources-guide","description":"Guide for finding external linked resources such as imaging, pathology, Minerva, HTAN, or other resource_* table links before declaring data unavailable"},{"uri":"cbioportal://gene-resolution-guide","description":"Guide for resolving ambiguous gene symbols, aliases, gene families, and shorthand such as CD3 before querying expression or alteration data"},{"uri":"cbioportal://study-resolution-guide","description":"Guide for resolving requested studies, avoiding silent substitute cohorts, and redirecting to known external cBioPortal instances when data is not in this deployment"},{"uri":"cbioportal://germline-guide","description":"Guide for querying germline variant data — storage columns, study discovery, query patterns, and somatic vs germline considerations"},{"uri":"cbioportal://study-guide/{study_id}","description":"Dynamic study-specific guide - use get_study_guide(study_id) tool to generate"}]}

▶ read_guide
{
 "uri": "cbioportal://statistical-tests-guide"
}

◀ result
Statistical Test Selection Guide
================================

Purpose
-------
This guide ensures the correct statistical test is selected before performing any group comparison, matching cBioPortal's own Group Comparison defaults.

HARD RULES — NEVER FABRICATE A STATISTIC
----------------------------------------
ClickHouse cannot run statistical tests. The agent therefore must NEVER produce a derived statistic that is not a literal column value from a SQL result. Specifically:

1. **Never invent a p-value.** Not "p < 0.001", not "p ≈ 0.05", not any p-value. If the user asks "what is the p-value?", the answer is *"I can't compute that — here is the 2x2 contingency table (or group statistics). Run it in cBioPortal's Group Comparison tab, in R with `fisher.test(...)` / `wilcox.test(...)`, or in Python with `scipy.stats.fisher_exact(...)` / `mannwhitneyu(...)`."*
2. **Never claim mutual exclusivity (or co-occurrence) from a contingency table alone.** A 2x2 table is not a test. The shape "altered/not altered × group A/group B" needs Fisher's exact + a defined direction (odds ratio < 1 with significant p). Without that test, the agent presents the table and stops. Descriptive phrasing is also a claim: "largely/mostly mutually exclusive", "rarely co-occur", "tend to co-occur" are forbidden without the test — point to cBioPortal's Mutual Exclusivity tab instead.
3. **Never report a "median" that came from `AVG(...)` or any non-median aggregate.** "Median" and "mean" are different statistics; for skewed clinical distributions (especially survival) they differ substantially. Use ClickHouse's `quantile(0.5)(...)` for actual median, and label arithmetic averages as "mean", never "median".
4. **Never report a hazard ratio, odds ratio, risk ratio, or relative risk** that wasn't computed by an external tool. These require regression / model fitting that ClickHouse does not do.
5. **Never report median overall survival from `AVG(OS_MONTHS)` or even `quantile(0.5)(OS_MONTHS)`.** Median OS requires Kaplan-Meier estimation, which handles censoring (`OS_STATUS = 0:LIVING` means the event hasn't happened yet). Naive medians/means over `OS_MONTHS` ignore censoring and are systematically wrong. The correct handoff: return the raw `(OS_MONTHS, OS_STATUS)` pairs (or descriptive counts: N events, N censored, follow-up range) and tell the user to run KM in R (`survival::survfit`) or Python (`lifelines.KaplanMeierFitter`), or use cBioPortal's Survival comparison.

If asked to do any of (1)–(5), respond with the appropriate handoff template from the "Approved Response Templates" section below — do not produce the number.

Ambiguous-Term Clarification (before any analysis)
--------------------------------------------------
If the user's question uses an ambiguous term, ask before computing anything. Examples:

- **"aggressive"** → could mean shorter overall survival, higher metastasis rate, higher grade/stage, higher TMB, or specific molecular features. Ask which definit … (9984 more chars)

▶ read_guide
{
 "uri": "cbioportal://common-pitfalls#16"
}

▶ read_guide
{
 "uri": "cbioportal://gene-expression-guide"
}

◀ result
### 16. 🚨 SILENT QUERY SUBSTITUTION ("did you mean...")

When the user's wording differs from canonical terminology (e.g. "V600V" looks like "V600E" with a typo, or "point mutation" sounds like "missense"), it is forbidden to silently rewrite the question and answer the rewritten version. Doing so produces an answer that looks confident but is for a different question — the user cannot tell what was changed.

#### ❌ Wrong: silently substitute

> User: *"Find patients in colorectal cancer with the V600V alteration in BRAF"*
> Agent: *(internally treats this as V600E)* "I found 412 samples with BRAF V600E in colorectal studies..."

> User: *"What is the most prevalent TP53 mutation in uterine cancer that is not a point mutation?"*
> Agent: *(internally treats "point mutation" = "missense", silently excludes only missense)* "The most prevalent non-missense TP53 mutation is..."

#### ✅ Correct: answer the literal question, flag any normalization

For an unusual-looking variant the user may have typed deliberately:
- Query for what was asked, literally.
- If 0 rows come back, **explain *why* zero is the expected answer** before suggesting a likely-intended alternative. For synonymous variants (e.g. BRAF V600V, TP53 R175R), the explanation is: *cBioPortal's mutation tables filter out synonymous (silent) variants in most studies, so 0 hits means "filtered upstream", not "no such variant exists in any patient"*. Then ask: *"Did you mean V600E (the canonical activating variant)? Or would you like me to look for V600V in the studies that do retain synonymous calls?"*
- If the wording is ambiguous (e.g. "point mutation"), ask the user which definition they meant before querying — do not pick one silently.

#### Mutation-type terminology mapping (use this to disambiguate)

| User says | Canonical definition | `mutation_type` filter |
|---|---|---|
| "point mutation" | Any SNV (single-nucleotide variant) — includes missense, nonsense, synonymous, splice-site SNVs | `mutation_type IN ('Missense_Mutation','Nonsense_Mutation','Silent','Splice_Site')` — **but ask the user to confirm scope first** |
| "missense" | Single amino-acid substitution that changes the protein | `mutation_type = 'Missense_Mutation'` |
| "nonsense" / "stop-gain" | Premature stop codon | `mutation_type = 'Nonsense_Mutation'` |
| "synonymous" / "silent" | Nucleotide change with no amino-acid change | `mutation_type = 'Silent'` (**often filtered out of public datasets** — see below) |
| "splice site" | Mutation in canonical splice acceptor/donor | `mutation_type = 'Splice_Site'` |
| "frameshift" | Indel changing reading frame | `mutation_type IN ('Frame_Shift_Ins','Frame_Shift_Del')` |
| "indel" / "in-frame" | In-frame insertion or deletion | `mutation_type IN ('In_Frame_Ins','In_Frame_Del')` |
| "truncating" | Anything that disrupts the protein early | `mutation_type IN ('Nonsense_Mutation','Frame_Shift_Ins','Frame_Shift_Del','Splice_Site','Nonstop_Mutation')` |

**Synonymous-variant filter. … (785 more chars)

◀ result
# Gene Expression Analysis Guide

This guide covers continuous-value genomic data: gene **expression**, **copy number** values, **methylation**, and related profile types. Mutation/CNA/SV *frequency* analysis lives in `cbioportal://mutation-frequency-guide`.

## Where this data lives

Continuous per-sample-per-gene values are stored in `genetic_alteration_derived`:

| Column | Description |
|---|---|
| `sample_unique_id` | `<study>_<sample_stable_id>` |
| `cancer_study_identifier` | study scope |
| `hugo_gene_symbol` | gene |
| `profile_type` | which assay/normalization (see below) |
| `alteration_value` | the actual value — stored as Nullable(String); cast with `toFloat64OrNull` |

`alteration_value` is a string because the same column hosts many different value scales. The `''` and `'NA'` sentinels mean "missing"; always filter them out and use `toFloat64OrNull(alteration_value) IS NOT NULL` for downstream math.

## Discovering profile types for a study

Different studies expose different profile types depending on what assays were run and how the data was normalized. Always check what a specific study supports before picking one:

```sql
SELECT DISTINCT profile_type
FROM genetic_alteration_derived
WHERE cancer_study_identifier = 'brca_metabric'
ORDER BY profile_type;
```

Common values across the public portal:

| Family | Profile types |
|---|---|
| mRNA expression | `mrna`, `mrna_median_Zscores`, `mrna_seq_v2_rsem`, `mrna_seq_v2_rsem_Zscores`, `mrna_seq_cpm`, `mrna_seq_fpkm`, `mrna_U133`, `mrna_outliers` |
| Copy number (continuous) | `cna`, `linear_CNA`, `log2CNA`, `cna_consensus`, `cna_rae`, `gistic` |
| Methylation | `methylation_hm27`, `methylation_hm450`, `methylation_epic`, `methylation_promoters_rrbs` |
| miRNA | `mirna`, `mirna_median_Zscores` |
| Protein | `protein_quantification`, `protein_level`, `RPPA` |

**Z-score vs raw choice.** When the user asks "is X correlated with Y", either works for Spearman (rank-based) — Pearson would care. Default to the non-Z-score variant if both exist, and call out which one in the response.

## Canonical recipe — Spearman correlation between two genes

```sql
SELECT *
FROM gene_pair_coexpression(
    study        = 'brca_metabric',
    gene_a       = 'TP53',
    gene_b       = 'MYC',
    profile_type = 'mrna'
);
```

Returns one row: `(gene_a, gene_b, profile_type, spearman_correlation, num_samples)`.

- `spearman_correlation` in [−1, 1]; `NULL` when fewer than 3 valid paired samples.
- Mirrors cbioportal-backend's `ClickhouseCoExpressionMapper.getCoExpressions`, simplified to a pair lookup (the backend computes one ref gene vs ALL other genes for the coexpression page; here the agent asks about a specific pair).

### Verified examples

| Study | gene_a | gene_b | profile_type | spearman | n |
|---|---|---|---|---|---|
| `brca_metabric` | TP53 | MYC | `mrna` | 0.118 | 1980 |
| `brca_metabric` | ESR1 | PGR | `mrna` | 0.487 | 1980 |

ESR1↔PGR is the textbook breast-cancer estrogen-receptor coregula … (2785 more chars)

▶ 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": "SELECT DISTINCT profile_type FROM genetic_alteration_derived WHERE cancer_study_identifier = 'brca_tcga_pan_can_atlas_2018' ORDER BY profile_type"
}

◀ result
{"rows":[{"profile_type":"gistic"},{"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"},{"profile_type":"rna_seq_v2_mrna_median_all_sample_Zscores"},{"profile_type":"rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores"},{"profile_type":"rppa"},{"profile_type":"rppa_Zscores"}]}

▶ clickhouse_run_select_query
{
 "query": "
WITH trunc_samples AS (
  SELECT DISTINCT sample_unique_id
  FROM genomic_event_derived
  WHERE cancer_study_identifier = 'brca_tcga_pan_can_atlas_2018'
    AND hugo_gene_symbol = 'TP53'
    AND variant_type = 'mutation'
    AND mutation_status != 'UNCALLED'
    AND off_panel = 0
    AND mutation_type IN ('Nonsense_Mutation','Frame_Shift_Ins','Frame_Shift_Del','Splice_Site','Nonstop_Mutation')
),
tp53_mut_any AS (
  SELECT DISTINCT sample_unique_id
  FROM genomic_event_derived
  WHERE cancer_study_identifier = 'brca_tcga_pan_can_atlas_2018'
    AND hugo_gene_symbol = 'TP53'
    AND variant_type = 'mutation'
    AND mutation_status != 'UNCALLED'
    AND off_panel = 0
),
expr AS (
  SELECT sample_unique_id, toFloat64OrNull(alteration_value) AS v
  FROM genetic_alteration_derived
  WHERE cancer_study_identifier = 'brca_tcga_pan_can_atlas_2018'
    AND profile_type = 'rna_seq_v2_mrna'
    AND hugo_gene_symbol = 'TP53'
    AND alteration_value NOT IN ('', 'NA')
    AND toFloat64OrNull(alteration_value) IS NOT NULL
)
SELECT
  'Truncating' AS group_name,
  count() AS n,
  avg(log2(e.v+1)) AS mean_log2_expr,
  quantile(0.5)(log2(e.v+1)) AS median_log2_expr,
  stddevSamp(log2(e.v+1)) AS sd_log2_expr
FROM expr e
INNER JOIN trunc_samples t USING (sample_unique_id)

UNION ALL

SELECT
  'WildType (no TP53 mutation)' AS group_name,
  count() AS n,
  avg(log2(e.v+1)) AS mean_log2_expr,
  quantile(0.5)(log2(e.v+1)) AS median_log2_expr,
  stddevSamp(log2(e.v+1)) AS sd_log2_expr
FROM expr e
LEFT JOIN tp53_mut_any m USING (sample_unique_id)
WHERE m.sample_unique_id IS NULL
"
}

◀ result
{"rows":[{"group_name":"WildType (no TP53 mutation)","n":0},{"group_name":"Truncating","n":131,"mean_log2_expr":9.161375768390078,"median_log2_expr":9.052130557166487,"sd_log2_expr":0.8969419158094935}]}

▶ clickhouse_run_select_query
{
 "query": "
WITH tp53_mut_any AS (
  SELECT DISTINCT sample_unique_id
  FROM genomic_event_derived
  WHERE cancer_study_identifier = 'brca_tcga_pan_can_atlas_2018'
    AND hugo_gene_symbol = 'TP53'
    AND variant_type = 'mutation'
    AND mutation_status != 'UNCALLED'
    AND off_panel = 0
),
expr AS (
  SELECT sample_unique_id, toFloat64OrNull(alteration_value) AS v
  FROM genetic_alteration_derived
  WHERE cancer_study_identifier = 'brca_tcga_pan_can_atlas_2018'
    AND profile_type = 'rna_seq_v2_mrna'
    AND hugo_gene_symbol = 'TP53'
    AND alteration_value NOT IN ('', 'NA')
    AND toFloat64OrNull(alteration_value) IS NOT NULL
)
SELECT
  count() AS n,
  avg(log2(v+1)) AS mean_log2_expr,
  quantile(0.5)(log2(v+1)) AS median_log2_expr,
  stddevSamp(log2(v+1)) AS sd_log2_expr
FROM expr
WHERE sample_unique_id NOT IN (SELECT sample_unique_id FROM tp53_mut_any)
"
}

◀ result
{"rows":[{"n":735,"mean_log2_expr":10.580482845733934,"median_log2_expr":10.632395463734442,"sd_log2_expr":0.6388909780036678}]}

▶ resolve_and_route
{
 "studyIds": [
  "brca_tcga_pan_can_atlas_2018"
 ]
}

◀ result
{"success":true,"message":"Found 1 study. Use the metadata to call the appropriate navigation tool(s).","data":{"totalCount":1,"studiesWithMetadata":[{"studyId":"brca_tcga_pan_can_atlas_2018","name":"Breast Invasive Carcinoma (TCGA, PanCancer Atlas)","sampleCount":1084,"studyViewUrl":"https://www.cbioportal.org/study?id=brca_tcga_pan_can_atlas_2018","metadata":{"clinicalAttributeIds":["AGE","AJCC_PATHOLOGIC_TUMOR_STAGE","AJCC_STAGING_EDITION","ANEUPLOIDY_SCORE","BUFFA_HYPOXIA_SCORE","CANCER_TYPE","CANCER_TYPE_ACRONYM","CANCER_TYPE_DETAILED","DAYS_LAST_FOLLOWUP","DAYS_TO_BIRTH","DAYS_TO_INITIAL_PATHOLOGIC_DIAGNOSIS","DFS_MONTHS","DFS_STATUS","DSS_MONTHS","DSS_STATUS","ETHNICITY","FORM_COMPLETION_DATE","FRACTION_GENOME_ALTERED","GENETIC_ANCESTRY_LABEL","GRADE","HISTORY_NEOADJUVANT_TRTYN","ICD_10","ICD_O_3_HISTOLOGY","ICD_O_3_SITE","INFORMED_CONSENT_VERIFIED","IN_PANCANPATHWAYS_FREEZE","MSI_SCORE_MANTIS","MSI_SENSOR_SCORE","MUTATION_COUNT","NEW_TUMOR_EVENT_AFTER_INITIAL_TREATMENT","ONCOTREE_CODE","OS_MONTHS","OS_STATUS","OTHER_PATIENT_ID","PATH_M_STAGE","PATH_N_STAGE","PATH_T_STAGE","PERSON_NEOPLASM_CANCER_STATUS","PFS_MONTHS","PFS_STATUS","PRIMARY_LYMPH_NODE_PRESENTATION_ASSESSMENT","PRIOR_DX","RACE","RADIATION_THERAPY","RAGNUM_HYPOXIA_SCORE","SAMPLE_COUNT","SAMPLE_TYPE","SEX","SOMATIC_STATUS","SUBTYPE","TBL_SCORE","TISSUE_PROSPECTIVE_COLLECTION_INDICATOR","TISSUE_RETROSPECTIVE_COLLECTION_INDICATOR","TISSUE_SOURCE_SITE","TISSUE_SOURCE_SITE_CODE","TMB_NONSYNONYMOUS","TUMOR_TISSUE_SITE","TUMOR_TYPE","WEIGHT","WINTER_HYPOXIA_SCORE"],"molecularProfileIds":["brca_tcga_pan_can_atlas_2018_gistic","brca_tcga_pan_can_atlas_2018_log2CNA","brca_tcga_pan_can_atlas_2018_mutations","brca_tcga_pan_can_atlas_2018_protein_quantification","brca_tcga_pan_can_atlas_2018_protein_quantification_zscores","brca_tcga_pan_can_atlas_2018_rna_seq_v2_mrna","brca_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","brca_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","brca_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores","brca_tcga_pan_can_atlas_2018_rppa","brca_tcga_pan_can_atlas_2018_rppa_Zscores","brca_tcga_pan_can_atlas_2018_structural_variants"],"genericAssayProfiles":["brca_tcga_pan_can_atlas_2018_armlevel_cna","brca_tcga_pan_can_atlas_2018_genetic_ancestry","brca_tcga_pan_can_atlas_2018_methylation_hm27_hm450_merge","brca_tcga_pan_can_atlas_2018_methylation_hm450","brca_tcga_pan_can_atlas_2018_phosphoprotein_quantification"],"heatmapProfileIds":["brca_tcga_pan_can_atlas_2018_protein_quantification_zscores","brca_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_Zscores","brca_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_Zscores","brca_tcga_pan_can_atlas_2018_rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores","brca_tcga_pan_can_atlas_2018_rppa_Zscores"],"availableComparisonTabs":["overlap","clinical","survival","alterations","mutations","mrna","protein","generic_assay_armlevel_cna","generic_assay_genetic_anc … (83 more chars)

▶ navigate_to_group_comparison
{
 "studyIds": [
  "brca_tcga_pan_can_atlas_2018"
 ],
 "groups": [
  {
   "name": "TP53 Truncating",
   "studyViewFilter": {
    "mutationDataFilters": [
     {
      "hugoGeneSymbol": "TP53",
      "profileType": "mutations",
      "categorization": "MUTATION_TYPE",
      "values": [
       [
        {
         "value": "Nonsense_Mutation"
        }
       ],
       [
        {
         "value": "Frame_Shift_Ins"
        }
       ],
       [
        {
         "value": "Frame_Shift_Del"
        }
       ],
       [
        {
         "value": "Splice_Site"
        }
       ],
       [
        {
         "value": "Nonstop_Mutation"
        }
       ]
      ]
     }
    ]
   }
  },
  {
   "name": "TP53 Wild-type",
   "studyViewFilter": {
    "mutationDataFilters": [
     {
      "hugoGeneSymbol": "TP53",
      "profileType": "mutations",
      "categorization": "MUTATED",
      "values": [
       [
        {
         "value": "NOT_MUTATED"
        }
       ]
      ]
     }
    ]
   }
  }
 ],
 "tab": "comparison/mrna",
 "selectedGene": "TP53"
}

◀ result
{"success":false,"error":"No samples found for group \"TP53 Truncating\" — filter may be too restrictive","details":{}}

▶ get_studyviewfilter_options
{
 "studyId": "brca_tcga_pan_can_atlas_2018",
 "geneSpecificQueries": [
  {
   "hugoGeneSymbol": "TP53",
   "profileType": "mutations"
  }
 ]
}

◀ result
{"success":true,"message":"Successfully retrieved StudyView filter options","data":{"studyId":"brca_tcga_pan_can_atlas_2018","geneSpecificCounts":[{"hugoGeneSymbol":"TP53","profileType":"mutations","counts":[{"value":"Missense_Mutation","label":"Missense Mutation","count":216},{"value":"Frame_Shift_Del","label":"Frame Shift Del","count":47},{"value":"In_Frame_Del","label":"In Frame Del","count":5},{"value":"Splice_Region","label":"Splice Region","count":1},{"value":"Frame_Shift_Ins","label":"Frame Shift Ins","count":14},{"value":"Splice_Site","label":"Splice Site","count":24},{"value":"Nonsense_Mutation","label":"Nonsense Mutation","count":46}]}]}}

▶ navigate_to_group_comparison
{
 "studyIds": [
  "brca_tcga_pan_can_atlas_2018"
 ],
 "groups": [
  {
   "name": "TP53 Truncating",
   "studyViewFilter": {
    "mutationDataFilters": [
     {
      "hugoGeneSymbol": "TP53",
      "profileType": "mutations",
      "categorization": "MUTATION_TYPE",
      "values": [
       [
        {
         "value": "Nonsense_Mutation"
        },
        {
         "value": "Frame_Shift_Ins"
        },
        {
         "value": "Frame_Shift_Del"
        },
        {
         "value": "Splice_Site"
        }
       ]
      ]
     }
    ]
   }
  },
  {
   "name": "TP53 Wild-type",
   "studyViewFilter": {
    "mutationDataFilters": [
     {
      "hugoGeneSymbol": "TP53",
      "profileType": "mutations",
      "categorization": "MUTATED",
      "values": [
       [
        {
         "value": "NOT_MUTATED"
        }
       ]
      ]
     }
    ]
   }
  }
 ],
 "tab": "comparison/mrna",
 "selectedGene": "TP53"
}

◀ result
{"success":true,"message":"Navigating to https://www.cbioportal.org/comparison/comparison/mrna?comparisonId=6ab521dec2115c492d884c29&selectedGene=TP53","url":"https://www.cbioportal.org/comparison/comparison/mrna?comparisonId=6ab521dec2115c492d884c29&selectedGene=TP53","data":{"description":"Group comparison (2 custom groups)","studies":["brca_tcga_pan_can_atlas_2018"],"totalGroups":2,"groups":[{"name":"TP53 Truncating","sampleCount":131},{"name":"TP53 Wild-type","sampleCount":719}],"studyViewUrl":"https://www.cbioportal.org/study?id=brca_tcga_pan_can_atlas_2018","groupUrls":[{"groupName":"TP53 Truncating","url":"https://www.cbioportal.org/study?id=brca_tcga_pan_can_atlas_2018#filterJson=%7B%22mutationDataFilters%22%3A%5B%7B%22hugoGeneSymbol%22%3A%22TP53%22%2C%22profileType%22%3A%22mutations%22%2C%22categorization%22%3A%22MUTATION_TYPE%22%2C%22values%22%3A%5B%5B%7B%22value%22%3A%22Nonsense_Mutation%22%7D%2C%7B%22value%22%3A%22Frame_Shift_Ins%22%7D%2C%7B%22value%22%3A%22Frame_Shift_Del%22%7D%2C%7B%22value%22%3A%22Splice_Site%22%7D%5D%5D%7D%5D%7D"},{"groupName":"TP53 Wild-type","url":"https://www.cbioportal.org/study?id=brca_tcga_pan_can_atlas_2018#filterJson=%7B%22mutationDataFilters%22%3A%5B%7B%22hugoGeneSymbol%22%3A%22TP53%22%2C%22profileType%22%3A%22mutations%22%2C%22categorization%22%3A%22MUTATED%22%2C%22values%22%3A%5B%5B%7B%22value%22%3A%22NOT_MUTATED%22%7D%5D%5D%7D%5D%7D"}]}}

═ answer (success)
This confirms the group sizes (131 truncating, 719 wild-type — close to my SQL count of 735, the small difference likely reflecting mutation-profiling denominator nuances between the two counting methods).

**[View mRNA Comparison: TP53 Truncating vs. Wild-type (BRCA TCGA PanCancer Atlas)](https://www.cbioportal.org/comparison/comparison/mrna?comparisonId=6ab521dec2115c492d884c29&selectedGene=TP53)**

This opens cBioPortal's Group Comparison → mRNA tab, which will show the box plots for TP53 expression across both groups along with the built-in significance test (t-test/Wilcoxon) computed by cBioPortal itself.

- **TP53 Truncating** (Nonsense, Frame_Shift_Ins/Del, Splice_Site): 131 samples
- **TP53 Wild-type** (no TP53 mutation): 719 samples

**Summary:** My own descriptive stats (mean log2 RSEM: 9.16 truncating vs. 10.58 wild-type) suggest lower expression in the truncating-mutant group, consistent with nonsense-mediated decay — but I have not run a statistical test myself. Use the linked cBioPortal comparison view (or `scipy.stats.ttest_ind` / R `t.test` on the raw values) to obtain the actual significance test and p-value.