Somatic mutations of the NIH FPDMM cohort. (A) Somatic mutation landscape depicting CHIP genes, AML-driver genes, and recurrently mutated genes. Each column is a patient; patients with hematologic malignancy are highlighted in red. The center heat map shows somatic mutation distribution; mutation types are represented with specific colors, as described by legends at the bottom right. Each row is a gene; genes belonging to CHIP and AML-driver genes are highlighted in red. The next heat map (top) shows annotated demographic and clinical information, which are also color-coded, as described by the legends at the right-hand side. The top bar plot shows the total somatic mutation numbers in each patient, with coding region mutations marked with colors used in the middle heat map and the noncoding region mutations colored in gray. The bar plot on the right of the middle heat map shows aggregated somatic mutation numbers for each gene, with color coding for mutation types. The bottom bar plot shows the percentage of the different base-changes (C>T, C>G, etc) in each patient. (B) Correlation between patients’ age at the time of sampling and the total number of somatic mutations. Only samples with fibroblast controls are included. Each dot in the graph represents the number of somatic mutations in 1 sequenced sample from a patient at the indicated age, and the color indicates the type of RUNX1 germline mutation in that patient. (C) Functional enrichment analysis of all somatically mutated genes. B/LB, benign/likely benign; CNV, copy number variation; fib, fibroblast; InDel, insertion-deletion; ISTH-BAT, International Society on Thrombosis and Haemostasis Bleeding Assessment Tool; MPV, mean platelet volume; M(RUNT), mutation in RUNT domain; M(TAD), mutation in transactivation domain; N/FS, nonsense/frame shift; Plt, platelet; som, somatic.

Somatic mutations of the NIH FPDMM cohort. (A) Somatic mutation landscape depicting CHIP genes, AML-driver genes, and recurrently mutated genes. Each column is a patient; patients with hematologic malignancy are highlighted in red. The center heat map shows somatic mutation distribution; mutation types are represented with specific colors, as described by legends at the bottom right. Each row is a gene; genes belonging to CHIP and AML-driver genes are highlighted in red. The next heat map (top) shows annotated demographic and clinical information, which are also color-coded, as described by the legends at the right-hand side. The top bar plot shows the total somatic mutation numbers in each patient, with coding region mutations marked with colors used in the middle heat map and the noncoding region mutations colored in gray. The bar plot on the right of the middle heat map shows aggregated somatic mutation numbers for each gene, with color coding for mutation types. The bottom bar plot shows the percentage of the different base-changes (C>T, C>G, etc) in each patient. (B) Correlation between patients’ age at the time of sampling and the total number of somatic mutations. Only samples with fibroblast controls are included. Each dot in the graph represents the number of somatic mutations in 1 sequenced sample from a patient at the indicated age, and the color indicates the type of RUNX1 germline mutation in that patient. (C) Functional enrichment analysis of all somatically mutated genes. B/LB, benign/likely benign; CNV, copy number variation; fib, fibroblast; InDel, insertion-deletion; ISTH-BAT, International Society on Thrombosis and Haemostasis Bleeding Assessment Tool; MPV, mean platelet volume; M(RUNT), mutation in RUNT domain; M(TAD), mutation in transactivation domain; N/FS, nonsense/frame shift; Plt, platelet; som, somatic.

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