CELLO

Introduction

CELLO2 is an interactive web server to visualize curated clinical and somatic genomic information of longitudinally paired gliomas, and to explore the probability of developing treatment-induced hypermutation using models that we trained from the collected data. The app is hosted on shinyapps.io at http://www.wang-lab-hkust.com:3838/cello2.

The server is built in R and Shiny, and is right now under active updating. In this web site, you can:

Click Genes panel to explore genomic alterations and RNA expression of one specific gene;
Click Cases panel to explore clinical and genetic information of patients;
Click CELLO2 panel to explore the probability of developing treatment-induced hypermutation using models that we trained from the collected data;

In this page you can visualize the genomic alteration and RNA expression of one specific gene in the initial and recurrent tumors of glioma patients. It is also possible to link the changes in genomic alteration and/or gene expression with several important clinical features such as molecular subtype, pathological grade, grade progression and development of hypermutation.

Visualize genomic alteration and gene expression

In the left control panel, you can input the gene name, such as IDH1, then click submit. At the right side of the page, you will see two figures displaying the gene expression (upper panel) and genomic alteration (lower panel) in the cohort. By default, the figures are separated into two facets representing hypermutation status at recurrence. Select to group by Molecular_Subtype and we can see the gene expression data are shown in scatter plot, and each point represents the expression level of one sample, in the unit of log2 RPKM. The genomic alteration data are shown in a heatmap. It is clear to see that IDH1 mutation are present in all IDH-mutant-codel and IDH-mutant-non-codel patients but in none of the IDHwt patients:

Regarding genomic alteration, we included data for mutations, copy number alterations and several other important alterations such as FGFR3-TACC3 fusion, PTPRZ1-MET fusion, EGFR*vIII, *MET*ex14, *MGMT fusions and hypermutation (HM). For example, to check hypermutated samples in this cohort, you can simply type HM in the gene name box.

Group by clinical features for comparison

In addition to molecular subtype, we can also explore other clinical features. For example, enter MKI67 in the gene name box, and select to group by Hypermutation_at_recurrence, from the results we can see higher frequency of MKI67 overexpression in patients that develop hypermutation:

An additional useful feature is to show the longitudinal pairs in the gene expression plot. This will add a link between the initial and recurrent tumor of each patient. For example, if we check VEGFA expression and Grade_Progression, we will see significant elevation of VEGFA expression during grade progression:

In the cases panel, there is an overview of the cases, which shows the time point of each surgery as well as the overall survival. In the input box, one can input a patient ID to view the clinical data, somatic mutations, and copy number alterations.

The “CELLO2” panel performs imputation and prediction of hypermutation (HM) using clinical and genomic profiles.

“example” patients prediction

To make it easier to understand the process of imputation and prediction of hypermutation (HM), we create “example” button which enables users to access the predicted results of three patients.

Click the “example” button.
The “example” patients will be displayed in “Upload data”. The “NA” (not available data) will be highlighted by yellow.

Use CELLO2 to predict glioma evolution

CELLO2 contains curated clinical and somatic genomic information of longitudinally paired gliomas

Gene expression

Genomic alteration heatmap

Cases Overview

Clinical information

Mutations

Copy Number Alterations

Download data

Introduction

Visualize genomic alteration and gene expression

Group by clinical features for comparison

“example” patients prediction