Figure 1.

TNBC patient sample overview. A, REMARK diagram showing pre- and on-treatment sample accrual schema from patients with TNBC enrolled in two clinical trials [NCT02544987 (BCM) and NCT201404107 (WashU)] and treated with carboplatin and docetaxel in the neoadjuvant setting. *, <45% samples were later excluded from the analysis based on evidence from data quality control. B, Overview of available omics datasets from 59 patients (22 tumors with pCR and 37 tumors without pCR). Pathogenic BRCA1/2 and PALB2 mutation status, RCB, and patient race are indicated via color-coded annotation tracks. C, Venn diagram showing the overlap of gene IDs detected across multiple analytes and omics data profiled. SCNA, somatic copy-number alteration. D, Hallmark metabolism pathways are induced by chemotherapy exclusively at the protein level. Scatter plot shows signed −log₁₀ FDR from GSEA using the signed (by direction of change) −log₁₀P values from paired Wilcoxon signed rank tests comparing RNA (x-axis) and protein levels (y-axis) for on-treatment (cycle 1, day 3) samples to matching baseline samples (n = 14).E, MSigDB Hallmark metabolism pathways are elevated in baseline non-pCR tumors at the protein level, whereas immune and cell-cycle pathways are elevated in baseline pCR tumors at both RNA and protein levels. Scatter plot shows the signed −log₁₀ FDR values from GSEA using ranked lists of signed (by direction of change) −log₁₀P values from Wilcoxon rank sum tests comparing RNA (x-axis) and protein (y-axis) levels in non-pCR tumors to pCR tumors. F, Cell-cycle kinase targets and PTM-SigDB phosphosites associated with genotoxic stress are enriched in pCR tumors relative to non-pCR tumors at baseline. Volcano plot shows results from PTM-SEA using the signed −log₁₀P values from Wilcoxon rank sum tests comparing phosphosite levels in non-pCR tumors to pCR tumors. Red and blue dots indicate significant (FDR <0.05) posttranslational modification signatures.