Version 1.4.1

Minor fixes for usability in clusters app.

• Switches values of cluster information table to detection rate (rather than normalized expression) per gene
• Removes sidebar input options on the home page

Version 1.4

Updated clusters app with a new look and additional analysis functionalities.
Featuring a new landing page, as well as a cluster marker table and new heatmap column annotations.

---

Full list of changes to cluster app:

General

• Created a landing page to welcome users to the app, and to provide citation and dataset information
• Added a GPLv3.0 license to the Github page and landing page
• Added large titles to each tab page for clarity

(NEW) Cluster information Tab (formerly called "Expression table")

• Created a table displaying gene markers of a given cluster, which appears upon selection of a row in the cluster table
• Allowed the cluster table to display before genes are entered, i.e. for a general query of the dataset clusters

Cell types clustered by expression (Heatmap) Tab

• Added multiple options for heatmap column (i.e. cluster) annotations. Users can choose to annotate one or more of the following: cell class, timepoints, or region (Forebrain or Pons) of the cluster

Version 1.3

Updated clusters app with enhancements to user experience and a new analysis tab.
Featuring a heatmap clustering plot, improved gene validation (including annotation genes), and quicker loading time.

Updated GRN app with enhancements to user experience and a new analysis tab.
Featuring TF specificity tab, improved interpretability for plots.

---

Full list of changes to Clusters app:

General

• Displayed all genes in the annotation as choices for text box input, implemented improved gene input validation to differentiate between genes in the annotation with no data vs. genes not found in the annotation
• Significantly reduced initial loading time, due to implementation of a server-side selectizeInput() for processing the large number of gene inputs
• Allowed gene lists as .txt files to be uploaded to the app (full documentation available in the wiki)

Expression table tab

• Conditionally formatted expression cells according to their value (darker orange for expression values closer to 1, lighter for those closer to 0) for quicker comparison

Cell types clustered by expression tab (NEW)

• Displayed a heatmap hierarchically clustering input genes and cell types together by their mean expression within clusters
• Implemented checkbox selection of broad cell types in the sidebar

---

Full list of changes to GRN app:

General

• Added TF activity and specificity tab

Plots & Plot functionalities

Heatmap Tab

• Adjusted size of plot and angle of cluster labels for better interpretability

Time-series Tab

• Added time-series of cell-type proportion per brain region

TF Activity and Specificity Tab (NEW)

• Visualise TF specficity by TF or by Cluster
• By TF sub-tab: bar-plot of mean activity of selected TFs in each cluster in currently viewed data-set
• By Cluster sub-tab: scatter plot of activity of each active TF in the selected cluster (y-axis) vs in all other clusters (x-axis), table of top specific TFs in cluster ranked by fold change

Version 1.2

Added GRN app with new features and improved user experience.
Includes interactive plots with hover tooltips, input validation, bookmarking, visualisation of per-sample analysis datasets.

Updated Clusters app with additional functionalities.
Includes file upload for gene lists, input validation, bookmarking, new analysis tab, improved expression table.

---

Full list of changes to GRN app:

General

• Migrated GRN app from the brain_TF_app repository into Braindex
• Added ability to visualise per-sample SCENIC analysis
• Expanded TF input options to include all TFs queried in SCENIC analysis and added TF input validation
• Added custom Braindex CSS and formatting
• Updated labels, descriptions, instructions in the app
• Added ability to download visualisations in PDF form

Plots & Plot functionalities

GRN Tab

• Added new GRN visualisation via ggNet
• Added basic hover interaction
• Added ability to highlight targets genes in a pathway based on user input gene list

TF Target Info Tab

• Moved from the previous GRN tab into separate tab
• Added TF binding site motif logos for each target gene

Heatmap Tab

• Added TF activity heatmap per joint cluster in the joint Pons and Forebrain datasets
• Added option to view TF activity for all per-time-point clusters or to split heatmap by time-point in the joint Pons and Forebrain datasets

DR Plot Tab

• Added DR plot coloured by cluster with labelling
• Added option to select different dimensionality reduction methods

Time-series Tab

• Fixed hovering fuctionality

---

Full list of changes to Clusters app:

General

• Implemented file upload for gene lists with tsv and csv formats (optional, with sidebar toggle)
• Added file input validation by producing errors for genes not found in the dataset

Dendrogram tab

• Plotted bubble plots and labels separately to ensure alignment with dendrogram figure (regardless of gene name length)
• Increased maximum number of displayed genes to 20 (from 12)

Expression table tab

• Changed table formatting package (DT to reacTable)
• Changed font colour of cluster names to white when background palette colour is dark (increased readability)
• Altered order of gene columns to match order of user input
• Increase maximum number of displayed genes to 20 (from 12)

Time-series tab

• Set spikelines to always be "ON" in interactive plot, removed extraneous plotly buttons
• Added information on number of cells in each cluster & total in time point to hover tooltips in interactive plot
• Implemented dropdown selection menu for input genes to switch timecourse tab between inputs (changes dynamically with input)

Single cell expression by sample tab

• Implemented a warning message & better colour palette for timepoints with 0 expression throughout sample

Clusters ranked by expression tab (NEW)

• Displayed a new analysis tab to rank each cluster by their expression of selected gene(s)
• Created a toggle between viewing expression of the first gene and the mean of all input genes

Version 1.1

Update to existing clusters app with new features and improved user experience.
Includes interactive plots with hover tooltips, options to download displayed data, and additional dendrogram functionalities.

---

Full list of changes to cluster app:

Plots & Plot functionalities

• Allow plotting of up to 12 genes at a time in the dendrogram (increased from 6)
• Plot mean expression values over the selected set of genes on the dendrogram (optional, with a toggle switch)
• Move the table from below the dendrogram to a new tab ("Expression table") for better visibility
• Implement an interactive (Plotly) version of the timecourse plot (optional, with a toggle switch)
• Enable downloads of the timecourse plot and the expression table
• Implement hover tooltips in UMAP and tSNE plots coloured by cluster under "Single cell expression, by region"
• Add violin plots for "Single cell expression, by sample" within a sub-tab

Aesthetics & User interface

• Update sidebar input interface
• Adjust dendrogram hover tooltips for increased legibility & visibility
• Add loading animations to plots

Version 1

The clusters app contains data from the mouse atlas published in Jessa et al, Nature Genetics, 2019.