Precision Medicine Knowledgebase (PMKB)
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1 Precision Medicine Knowledgebase (PMKB) 3/513/ /The-cancer-precisionmedicine-knowledge-base-for
2 Click on this to expand/collapse side menu Home Page Mission and Site Summary Recent Additions to PMKB
3 Search for Genes
4 Browse Genes
5 Gene Page
6 Search for Variants Either search by variants through the gene page or on their own using either of the boxed regions above. Includes some copy number variants.
7 Browse Variants 513 Variants described in PMKB
8 Variant Page Coordinates for exon 20
9 Interpretations Scroll down to view latest interpretations
10 View Latest Interpretations At bottom of home page
11 Excel of All Interpretations Available for Download Columns include Genes, Tumor types, Variants, Tier, Interpretations, and Citations Each row represents an interpretation
12 Browse Interpretations Each interpretation is within disease context and may be specific to a variant(s). Click on interpretation to see interpretation page w/citations and more information.
13 Interpretation Page Links to PubMed
14 Tier Definitions Tier 1 - Clinical utility has been demonstrated - Actionable / Clinically Relevant variants. Variants in genes with approved therapeutic implications in specified tumors. Tier 2 - Clinical utility/actionability has diagnostic, prognostic or therapeutic implications. Variants with potential diagnostic/classification, prognostic implications. Variants with approved therapeutic implications in a different tumor type. Novel variants in genes that have approved therapeutic implications. Variants associated with Clinical trials. Tier 3 - Variants of Unknown Significance.
15 Search for Variants Linked to Tumor Type
16 Browse Tumor Types Click on tumor type to see all associated interpretations. 143 tumor types listed not all have interpretations.
17 Tumor-Specific Page of Interpretations
18 Search for Tissue type
19 Browse Tissue Types 68 tissue types listed not all have interpretations.
20 PMKB Bot Type in a gene name, disease, tissue, or variant PMKB Bot will output interpretations that fit your criteria. Click anywhere in the interpretation or the image above the interpretation to see the gene page housing that interpretation.
21 Scenario #1 You are a laboratory professional putting together a Pan Cancer gene list. Browse Genes and add all OR add only genes with interpretations
22 Browse Genes and sort genes by the number of associated interpretations.
23 Another way to compile the same list of genes with interpretations is to download the Excel file of all interpretations, sort by gene name, and expect duplicates for genes with >1 interpretation. I like to copy the gene column over to another worksheet/tab. One you have the gene list in Excel (or similar), go to Data/Remove Duplicates to have a full list of candidate genes. I like to alphabetize before integrating with other lists/resources.
24 Scenario #2 You are putting together a list for a potential AML NGS panel. Using PMKB, what genes might you consider including? Search for AML Tumor Type (see slides 14-16) Filter spreadsheet for rows/interpretations related to AML Copy Information over to new unprotected worksheet Filter Tumor Type(s) column by Contains criteria for Acute Myeloid Leukemia
25 Scenario #3 Your laboratory is interpreting a small NGS panel for a patient with lung adenosarcoma. How can PMKB aid in interpretation? Abnormal genes EGFR L858R RET V804M Normal genes ALK ERBB2 KRAS PIK3CA BRAF
26 PMKB Relevant Interpretations EGFR: positive for L858R mutation ERBB2: pertinent negative! nts/366 KRAS: pertinent negative! nts/368 PIK3CA: pertinent negative! nts/367
27 Future Features: Coming Soon! Shared API Opportunities for Crowd-sourcing: Addition of variants Addition of interpretation
28 Contacts Linda Huang PMKB Developer Olivier Elemento, PhD IPM Computational Biology Head and PMKB Project Supervision
CIViC Clinical Interpretations of Variants in Cancer. rnal/v49/n2/full/ng.3774.html
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Frequency(%) KRAS G12 KRAS G13 KRAS A146 KRAS Q61 KRAS K117N PIK3CA H1047 PIK3CA E545 PIK3CA E542K PIK3CA Q546. EGFR exon19 NFS-indel EGFR L858R
Frequency(%) 1 a b ALK FS-indel ALK R1Q HRAS Q61R HRAS G13R IDH R17K IDH R14Q MET exon14 SS-indel KIT D8Y KIT L76P KIT exon11 NFS-indel SMAD4 R361 IDH1 R13 CTNNB1 S37 CTNNB1 S4 AKT1 E17K ERBB D769H ERBB
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