update oncoprint legends

content/03.results.md

@@ -147,7 +147,7 @@ We observed somatic mutations or fusions in _NF2_ in 41% (7/17) of meningiomas,
 DNETs harbored alterations in MAPK/PI3K pathway genes, as was previously reported [@doi:10.1093/jnen/nlz101], including _FGFR1_ (21%, 4/19), _PDGFRA_ (10%, 2/19), and _BRAF_ (5%, 1/19).
 **Figure {@fig:S3}A** depicts frequent mutations in additional rare brain tumor histologies.
 
-![**Mutational landscape of PBTA tumors.** Shown are frequencies of canonical somatic gene mutations, CNVs, fusions, and TMB (top bar plot) for the top 20 genes mutated across primary tumors within the OpenPBTA dataset. A, Low-grade gliomas (N = 226): pilocytic astrocytoma (N = 104), other low-grade glioma (N = 68), ganglioglioma (N = 35), pleomorphic xanthoastrocytoma (N = 9), subependymal giant cell astrocytoma (N = 10); B, Embryonal tumors (N = 129): medulloblastoma (N = 95), atypical teratoid rhabdoid tumor (N = 24), other embryonal tumor (N = 10); C, High-grade gliomas (N = 63): diffuse midline glioma (N = 36) and other high-grade glioma (N = 27); D, Other CNS tumors (N = 153): ependymoma (N = 60), craniopharyngioma (N = 31), meningioma (N = 17), dysembryoplastic neuroepithelial tumor (N = 19), Ewing sarcoma (N = 7), schwannoma (N = 12), and neurofibroma plexiform (N = 7). Additional, rare CNS tumors are displayed in **Figure {@fig:S3}B**. Tumor histology (`Cancer Group`) and patient sex (`Germline sex estimate`) are displayed as annotations at the bottom of each plot. Only tumors with mutations in the listed genes are shown. Multiple CNVs are denoted as a complex event. N denotes the number of unique tumors with one tumor per patient used.](https://raw.githubusercontent.com/AlexsLemonade/OpenPBTA-analysis/2eb889d2d495a7327fb51e377df2f9d780c47117/figures/pngs/figure2.png?sanitize=true){#fig:Fig2 width="9in"}
+![**Mutational landscape of PBTA tumors.** Shown are frequencies of canonical somatic gene mutations, CNVs, fusions, and TMB (top bar plot) for the top mutated genes across primary tumors within the OpenPBTA dataset. A, Low-grade gliomas (N = 226): pilocytic astrocytoma (N = 104), other low-grade glioma (N = 68), ganglioglioma (N = 35), pleomorphic xanthoastrocytoma (N = 9), subependymal giant cell astrocytoma (N = 10); B, Embryonal tumors (N = 129): medulloblastoma (N = 95), atypical teratoid rhabdoid tumor (N = 24), other embryonal tumor (N = 10); C, High-grade gliomas (N = 63): diffuse midline glioma (N = 36) and other high-grade glioma (N = 27); D, Other CNS tumors (N = 153): ependymoma (N = 60), craniopharyngioma (N = 31), meningioma (N = 17), dysembryoplastic neuroepithelial tumor (N = 19), Ewing sarcoma (N = 7), schwannoma (N = 12), and neurofibroma plexiform (N = 7). Additional, rare CNS tumors are displayed in **Figure {@fig:S3}B**. Tumor histology (`Cancer Group`) and patient sex (`Germline sex estimate`) are displayed as annotations at the bottom of each plot. Only tumors with mutations in the listed genes are shown. Multiple CNVs are denoted as a complex event. N denotes the number of unique tumors with one tumor per patient used.](https://raw.githubusercontent.com/AlexsLemonade/OpenPBTA-analysis/2eb889d2d495a7327fb51e377df2f9d780c47117/figures/pngs/figure2.png?sanitize=true){#fig:Fig2 width="9in"}
 
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content/06.administrative.md

@@ -35,7 +35,7 @@ AJW is a member of the Scientific Advisory boards for Alexion and DayOne Biophar
 A, CBTN and PNOC collected tumors from 943 patients. 22 cell lines were created from tumor tissue, and over 2000 specimens were sequenced (N = 1035 RNA-Seq, N = 940 WGS, and N = 32 WXS or targeted panel). Data was harmonized by the Kids First Data Resource Center using an Amazon S3 framework within CAVATICA. B, Stacked bar plot summary of the number of biospecimens per phase of therapy. Each panel denotes a broad histology and each bar denotes a cancer group. (Abbreviations: GNG = ganglioglioma, Other LGG = other low-grade glioma, PA = pilocytic astrocytoma, PXA = pleomorphic xanthoastrocytoma, SEGA = subependymal giant cell astrocytoma, DIPG = diffuse intrinsic pontine glioma, DMG = diffuse midline glioma, Other HGG = other high-grade glioma, ATRT = atypical teratoid rhabdoid tumor, MB = medulloblastoma, Other ET = other embryonal tumor, EPN = ependymoma, PNF = plexiform neurofibroma, DNET = dysembryoplastic neuroepithelial tumor, CRANIO = craniopharyngioma, EWS = Ewing sarcoma, CPP = choroid plexus papilloma). Only tumors with available descriptors were included. C, Overview of the open analysis and manuscript contribution model. In the analysis GitHub repository, a contributor proposed an analysis, implemented it in their fork, and filed a pull request (PR) to add their changes to the analysis repository. PRs underwent review for scientific rigor and implementation correctness. Using container and continuous integration technologies, PRs were checked to ensure that all software dependencies were included and code was not sensitive to underlying data changes. Finally, a contributor filed a PR documenting their methods and results to the Manubot-powered manuscript repository for review. D, A potential path for an analytical PR. Arrows indicate revisions to a PR. Panel A created with [BioRender.com](biorender.com).
 
 **Figure 2. Mutational landscape of PBTA tumors.**
-Shown are frequencies of canonical somatic gene mutations, CNVs, fusions, and TMB (top bar plot) for the top 20 genes mutated across primary tumors within the OpenPBTA dataset. A, Low-grade gliomas (N = 226): pilocytic astrocytoma (N = 104), other low-grade glioma (N = 68), ganglioglioma (N = 35), pleomorphic xanthoastrocytoma (N = 9), subependymal giant cell astrocytoma (N = 10); B, Embryonal tumors (N = 129): medulloblastoma (N = 95), atypical teratoid rhabdoid tumor (N = 24), other embryonal tumor (N = 10); C, High-grade gliomas (N = 63): diffuse midline glioma (N = 36) and other high-grade glioma (N = 27); D, Other CNS tumors (N = 153): ependymoma (N = 60), craniopharyngioma (N = 31), meningioma (N = 17), dysembryoplastic neuroepithelial tumor (N = 19), Ewing sarcoma (N = 7), schwannoma (N = 12), and neurofibroma plexiform (N = 7). Additional, rare CNS tumors are displayed in **Figure {@fig:S3}B**. Tumor histology (`Cancer Group`) and patient sex (`Germline sex estimate`) are displayed as annotations at the bottom of each plot. Only tumors with mutations in the listed genes are shown. Multiple CNVs are denoted as a complex event. N denotes the number of unique tumors with one tumor per patient used.
+Shown are frequencies of canonical somatic gene mutations, CNVs, fusions, and TMB (top bar plot) for the top mutated genes across primary tumors within the OpenPBTA dataset. A, Low-grade gliomas (N = 226): pilocytic astrocytoma (N = 104), other low-grade glioma (N = 68), ganglioglioma (N = 35), pleomorphic xanthoastrocytoma (N = 9), subependymal giant cell astrocytoma (N = 10); B, Embryonal tumors (N = 129): medulloblastoma (N = 95), atypical teratoid rhabdoid tumor (N = 24), other embryonal tumor (N = 10); C, High-grade gliomas (N = 63): diffuse midline glioma (N = 36) and other high-grade glioma (N = 27); D, Other CNS tumors (N = 153): ependymoma (N = 60), craniopharyngioma (N = 31), meningioma (N = 17), dysembryoplastic neuroepithelial tumor (N = 19), Ewing sarcoma (N = 7), schwannoma (N = 12), and neurofibroma plexiform (N = 7). Additional, rare CNS tumors are displayed in **Figure {@fig:S3}B**. Tumor histology (`Cancer Group`) and patient sex (`Germline sex estimate`) are displayed as annotations at the bottom of each plot. Only tumors with mutations in the listed genes are shown. Multiple CNVs are denoted as a complex event. N denotes the number of unique tumors with one tumor per patient used.
 
 **Figure 3. Mutational co-occurrence and signatures highlight key oncogenic drivers.**
 A, Bar plot of occurrence and co-occurrence of nonsynonymous mutations for the 50 most commonly mutated genes across all tumor types, which are denoted as "Other" when there are fewer than 10 tumors per grouping; B, Co-occurrence and mutual exclusivity of nonsynonymous mutations between genes; The co-occurrence score is defined as $I(-\log_{10}(P))$ where $P$ is defined by Fisher's exact test and $I$ is 1 when mutations co-occur more often than expected and -1 when exclusivity is more common; C, The number of SV breaks significantly correlate with CNV breaks (Adjusted R = 0.443, p = 1.05e-38). D, Chromothripsis frequency across pediatric brain tumors for all cancer groups with N >= 3 tumors. E, Sina plots of RefSig signature weights for signatures 1, 11, 18, 19, 3, 8, N6, MMR2, and Other across cancer groups. Box plot represents 5% (lower whisker), 25% (lower box), 50% (median), 75% (upper box), and 95% (upper whisker) quantiles.

content/08.supplemental.md

@@ -4,7 +4,7 @@
 
 ![**Validation of Consensus SNV calls and Tumor Mutation Burden, Related to Figures 2 and 3.** Correlation (A) and violin (B) plots of mutation variant allele frequencies (VAFs) comparing the variant callers (Lancet, Strelka2, Mutect2, and VarDict) used for PBTA samples. Upset plot (C) showing overlap of variant calls. Correlation (D) and violin (E) plots of mutation variant allele frequencies (VAFs) comparing the variant callers (Lancet, Strelka2, and Mutect2) used for TCGA samples. Upset plot (F) showing overlap of variant calls. Violin plots (G) showing VAFs for Lancet calls performed on WGS and WXS from the same tumor (N = 52 samples from 13 patients). Cumulative distribution TMB plots for PBTA (H) and TCGA (I) tumors using consensus SNV calls.](https://raw.githubusercontent.com/AlexsLemonade/OpenPBTA-analysis/2eb889d2d495a7327fb51e377df2f9d780c47117/figures/pngs/figureS2.png?sanitize=true){#fig:S2 tag="S2" width="7in"}
 
-![**Genomic instability of pediatric brain tumors, Related to Figures 2 and 3.** (A) Violin plots of tumor purity by cancer group. Dots represent the group median. (B) Oncoprint of canonical somatic gene mutations, CNVs, fusions, and TMB (top bar plot) for the top 20 genes mutated across rare CNS tumors: desmoplastic infantile astrocytoma and ganglioglioma (N = 2), germinoma (N = 4), glial-neuronal NOS (N = 8), metastatic secondary tumors (N = 2), neurocytoma (N = 2), pineoblastoma (N = 4), Rosai-Dorfman disease (N = 2), and sarcomas (N = 4). Patient sex (`Germline sex estimate`) and tumor histology (`Cancer Group`) are displayed as annotations at the bottom of each plot. Multiple CNVs are denoted as a complex event. N denotes the number of unique tumors with one tumor per patient used. (C) Genome-wide plot of CNV alterations by broad histology. Each row represents one sample. Box and whisker plots of number of CNV breaks (D) or SV breaks (E) by number of chromothripsis regions. Box plot represents 5% (lower whisker), 25% (lower box), 50% (median), 75% (upper box), and 95% (upper whisker) quantiles.](https://raw.githubusercontent.com/AlexsLemonade/OpenPBTA-analysis/2eb889d2d495a7327fb51e377df2f9d780c47117/figures/pngs/figureS3.png?sanitize=true){#fig:S3 tag="S3" width="7in"}
+![**Genomic instability of pediatric brain tumors, Related to Figures 2 and 3.** (A) Violin plots of tumor purity by cancer group. Dots represent the group median. (B) Oncoprint of canonical somatic gene mutations, CNVs, fusions, and TMB (top bar plot) for the top mutated genes across rare CNS tumors: desmoplastic infantile astrocytoma and ganglioglioma (N = 2), germinoma (N = 4), glial-neuronal NOS (N = 8), metastatic secondary tumors (N = 2), neurocytoma (N = 2), pineoblastoma (N = 4), Rosai-Dorfman disease (N = 2), and sarcomas (N = 4). Patient sex (`Germline sex estimate`) and tumor histology (`Cancer Group`) are displayed as annotations at the bottom of each plot. Multiple CNVs are denoted as a complex event. N denotes the number of unique tumors with one tumor per patient used. (C) Genome-wide plot of CNV alterations by broad histology. Each row represents one sample. Box and whisker plots of number of CNV breaks (D) or SV breaks (E) by number of chromothripsis regions. Box plot represents 5% (lower whisker), 25% (lower box), 50% (median), 75% (upper box), and 95% (upper whisker) quantiles.](https://raw.githubusercontent.com/AlexsLemonade/OpenPBTA-analysis/2eb889d2d495a7327fb51e377df2f9d780c47117/figures/pngs/figureS3.png?sanitize=true){#fig:S3 tag="S3" width="7in"}
 
 ![**Mutational signatures in pediatric brain tumors, Related to Figure 3.** (A) Sample-specific RefSig signature weights across cancer groups ordered by decreasing Signature 1 exposure. (B) Proportion of Signature 1 plotted by phase of therapy for each cancer group.](https://raw.githubusercontent.com/AlexsLemonade/OpenPBTA-analysis/2eb889d2d495a7327fb51e377df2f9d780c47117/figures/pngs/figureS4.png?sanitize=true){#fig:S4 tag="S4" width="7in"}