This walk-through is intended to represent a typical workflow when building and studying a cohort of oncology cases.
- 2.Select the following studies to add to your cohort:
- 1.TCGA – BRCA – Breast Invasive Carcinoma
- 2.TCGA – Ovarian Serous Cystadenocarcinoma
- 3.Add a
Cohort Name= TCGA Breast and Ovarian_1472
- 4.Click on
Show query detailsto see the study makeup of your cohort.
Chartswill be open by default. If not, click
- 7.Use the gear icon in the top-right to change viewable chart settings.
Overall Survivalhave interesting data about this cohorts
Subjecttab with all Subjects list is displayed below Charts with a link to each Subject by ID and other high-level information, like Data Types measured and reported. By clicking a subject ID, you will be brought to the data collected at the Subject level.
- 9.Search for subject
TCGA-E2-A14Yand view the data about this Subject.
- 10.Click the
TCGA-E2-A14YSubject ID link to view clinical data for this Subject that was imported via the metadata.tsv file on ingest.
- 1.Note: the Subject is a 35 year old Female with vital status and other phenotypes that feed up into the
Subjectattribute selection criteria when creating or editing cohorts.
Xto close the Subject details.
Hide chartsto increase interactive landscape.
- 1.Click the
Marker Frequencytab, then click the
- 2.Review the gene list and mutation frequencies.
- 3.Note that PIK3CA has a high rate of mutation in the Cohort (ranked 2nd with 33% mutation frequency in 326 of the 987 Subjects that have Somatic Mutation data in this cohort).
- 1.Do Subjects with PIK3CA mutations have changes in PIK3CA RNA Expression?
- 4.Click the
Gene Expressiontab, search for
- 1.PIK3CA RNA is down-regulated in 27% of the subjects relative to normal samples.
- 1.Switch from
diseaseReference where the Subject’s denominator is the median of all disease samples in your cohort.
- 2.The count of matching vs. total subjects that have PIK3CA up-regulated RNA which may indicate a distinctive sub-phenotype.
- 5.Click directly on
PIK3CAgene link in the
- 6.You are brought to the
Genetab under the
Gene Summarysub-tab that lists information and links to public resources about PIK3CA.
- 7.Click the
Show legend and filtersif it does not open by default.
- 8.Below the interactive legend you see a set of analysis tracks: Needle Plot, Primate AI, Pathogenic variants, and Exons.
- 9.The Needle Plot allows toggling the plot by
Sample Count. Select
Sample Countin the
Plot bylegend above the plot.
- 1.There are 87 mutations distributed across the 1068 amino acid sequence, listed below the analysis tracks.
- 1.These can be exported via the icon into a table
- 10.We know that missense variants can severely disrupt translated protein activity. Deselect all
Variant Typesexcept for
Show Variant Typelegend above the needle plot.
- 1.Many mutations are in the functional domains of the protein as seen by the colored boxes and labels on the x-axis of the Needle Plot.
- 11.Hover over the variant with the highest sample count in the yellow
- 1.The pop-up shows variant details for the 64 Subjects observed with it: 63 in the Breast Cancer study and 1 in the Ovarian Cancer Study.
- 12.Use the Exon zoom bar from each end of the Amino Acid sequence to zoom in to the
PI3Kadomain to better separate observations.
- 13.There are three different missense mutations at this locus changing the wildtype Glutamine at different frequencies to Lysine (64), Glycine (6), or Alanine (2).
Pathogenic VariantTrack shows 7 ClinVar entries for mutations stacked at this locus affecting amino acid 545. Pop up details with pathogenicity calls, phenotypes, submitter and a link to the ClinVar entry is seen by hovering over the purple triangles.
- 15.Note the
Primate AItrack and high Primate AI score.
Primate AItrack displays Scores for potential missense variants, based on polymorphisms observed in primate species. Points above the dashed line for the 75th percentile may be considered "likely pathogenic" as cross-species sequence is highly conserved; you often see high conservancy at the functional domains. Points below the 25th percentile may be considered "likely benign".
- 16.Click the
Expressiontab and notice that normal Breast and normal Ovarian tissue have relatively high PIK3CA RNA Expression in GTex RNAseq tissue data but ubiquitously expressed.