incytr-viz 0.0.1

A browser-based tool to visualize and interact with signaling pathways returned InCytr.

Incytr Visualization

Install

PIP

Requires Python >= 3.10

*It is recommended to install this program in a virtual environment using tools such as venv or conda

pip install --upgrade incytr-viz

From Source

1. Clone repository and cd into repo directory
2. pip install .

Demo

This will download small demo files from Zenodo drawn from the 5XFAD Alzheimer's model dataset referenced in the manuscript and run the program automatically.

1. Run incytr-viz-demo in your console (no arguments required). If this does not work for you, you can download the file incytr_tutorial.zip manually from Zenodo, unzip the file, and proceed with the quickstart instructions below

2. After the pathways have loaded, navigate to http://127.0.0.1:8000/ in your web browser. Instructions on using the tool can be found in the "Help" section on the loaded page.

Quickstart

1. See Input Format section below for details on clusters and pathways files

2. Run incytr: incytr-viz --clusters path/to/clusters.csv --pathways path/to/pathways.csv

3. After pathways have loaded, navigate to http://127.0.0.1:8000/ in your web browser. Instructions on using the tool can be found in the "Help" section on the loaded page. Large datasets (~1M pathways) may take longer on initial load.

Use

Instructions on using the tool can be found in the "Help" section on the loaded page. You can also find the same information in this repository at src/incytr_viz/assets/help.md

Input Format

A. Clusters File

CSV or TSV with the names of experimental conditions and cell populations analyzed by incytr. Column names are case-insensitive

Important: Ensure that the entries in the "Condition" column in the clusters file match the condition names provided to incytr. Note the Sigprob_5X and SigProb_WT column headers in pathways file (below) align with "5X" and "WT" conditions in the clusters file.

Required columns:

• condition -- Name of experimental condition.
• type -- Name of cell population. Not all population types need to be present in both conditions.

Optional columns:

• population: number of cells for that condition and type. This is used only for sizing nodes in the network view

Note: running incytr-viz-demo will download an appropriately-formatted example input at incytr_viz_demo/clusters.csv

Example:

      +-----------+----------------------+--------------------+
      | Condition |         Type         |     Population     |
      +-----------+----------------------+--------------------+
      |    5X     |  Excitatory.neurons  |         8665       |
      |    5X     | Medium.spiny.neurons |         1590       |
      |    5X     |   Oligodendrocytes   |         2845       |
      |    5X     |  Endothelial.cells   |         311        |
      |    5X     |         OPCs         |         478        |
      |    5X     |      Microglia       |         1486       |
      |    WT     |  Excitatory.neurons  |         11718      |
      |    WT     |     Interneurons     |         2086       |
      |    WT     |      Astrocytes      |         1199       |
      |    WT     |  Endothelial.cells   |          480       |
      |    WT     |         OPCs         |          683       |
      |    WT     |      Microglia       |          803       |
      +-----------+----------------------+--------------------+

B. Pathways File

This file should be a CSV or TSV output previously generated by the incytr analysis package. Some columns are optional and are dependent on the data modalities available

Important: Ensure that the entries in the "Condition" column in the clusters file match the condition names provided to incytr. Note the Sigprob_5X and SigProb_WT column headers in pathways file (below) align with "5X" and "WT" conditions in the clusters file.

Required columns:

• path -- 4-step network with components separated by asterisks (e.g. ABC*D)
• sender -- sending cell population
• receiver -- receiving cell population
• sigprob_X -- signaling probability for experimental (positive aFC) condition ('X' will vary)
• sigprob_Y -- signaling probability for control (negative aFC) condition ('Y' will vary)
• afc -- adjusted fold change

*The left-most sigprob column should be the *

Optional columns:

• p_value_X ('X' will vary)
• p_value_Y ('Y' will vary)
• TPDS (transcriptomics-based pathway differential score)
• PPDS (proteomics-based pathway differential score)
• sik_r_of_em -- Signaling involved kinase relationship between receptor/effector (receptor is kinase, effector is substrate)
• sik_r_of_t -- Signaling involved kinase relationship between receptor/target gene
• sik_em_of_t -- Signaling involved kinase relationship between effector/target gene
• sik_em_of_r -- Signaling involved kinase relationship between effector/receptor
• sik_t_of_r -- Signaling involved kinase relationship between target gene/receptor
• sik_t_of_em -- Signaling involved kinase relationship between target gene/effector
• umap1 -- optional first 2-d umap coordinate for pathway
• umap2 -- optional second 2-d umap coordinate for pathway

Note: running incytr-viz-demo will also download an appropriately-formatted example input at incytr_viz_demo/pathways.csv

Example (with all required and optional columns):

+---+------------------------+--------------------+--------------------+-------------+-------------+--------------+      \
|   |          Path          |       Sender       |      Receiver      | SigProb_5X  | SigProb_WT  |     aFC      |      \
+---+------------------------+--------------------+--------------------+-------------+-------------+--------------+      \
| 0 |  Cntn4*App*Aak1*Dock7  | Excitatory.neurons | Excitatory.neurons | 0.819899544 | 0.465168271 | 0.816354872  |      \
| 1 |  Cntn4*App*Aak1*Etl4   | Excitatory.neurons | Excitatory.neurons | 0.886444905 | 0.890006529 | -0.005778447 |      \
| 2 |  Cntn4*App*Aak1*Stk39  | Excitatory.neurons | Excitatory.neurons | 0.293952701 | 0.243354205 | 0.098756719  |      \
| 3 |   Cntn4*App*Aak1*Syp   | Excitatory.neurons | Excitatory.neurons | 0.909707784 | 0.922833896 | -0.020645266 |      \
| 4 |  Cntn4*App*Aak1*Basp1  | Excitatory.neurons | Excitatory.neurons | 0.863494378 | 0.878796052 | -0.025312546 |      \
| 5 |  Cntn4*App*Aak1*Rph3a  | Excitatory.neurons | Interneurons | 0.826835011 | 0.76565119  | 0.110772934  |            \
| 6 |  Cntn4*App*Aak1*Mark2  | Excitatory.neurons | Interneurons | 0.42778563  | 0.359672825 | 0.159537491  |            \
| 7 | Cntn4*App*Aak1*Pitpnm2 | Excitatory.neurons | Interneurons | 0.824016257 | 0.494738382 | 0.734843587  |            \
| 8 | Cntn4*App*Aak1*Slc2a3  | Excitatory.neurons | Interneurons | 0.489517379 | 0.752109522 | -0.618555434 |            \
+---+------------------------+--------------------+--------------------+-------------+-------------+--------------+      \


+---+------------+------------+-------------+------------+-------------+-------------+------------+-------------+ \
|   | p_value_5X | p_value_WT | SiK_R_of_EM | SiK_R_of_T | SiK_EM_of_T | SiK_EM_of_R | SiK_T_of_R | SiK_T_of_EM | \
+---+------------+------------+-------------+------------+-------------+-------------+------------+-------------+ \
| 0 |     0      |     0      |             |            |    Aak1     |             |            |             | \
| 1 |     0.01   |     .1     |             |            |    Aak1     |             |            |             | \
| 2 |     0      |     0      |             |            |    Aak1     |             |            |    Stk39    | \
| 3 |     0      |     0      |             |            |    Aak1     |             |            |             | \
| 4 |     1      |     1      |             |            |    Aak1     |             |            |             | \
| 5 |     0      |     0      |             |            |    Aak1     |             |            |             | \
| 6 |     0      |     0      |             |            |    Aak1     |             |            |    Mark2    | \
| 7 |     0      |     0      |             |            |    Aak1     |             |            |             | \
| 8 |     0      |     0      |             |            |    Aak1     |             |            |             | \
+---+------------+------------+-------------+------------+-------------+-------------+------------+-------------+ \

+---+--------------+--------------+-----------+-----------+
|   |     TPDS     |     PPDS     |   umap1   |   umap2   |
+---+--------------+--------------+-----------+-----------+
| 0 | 0.673081017  | -0.077709086 | 12.823026 | -1.528055 |
| 1 | -0.005778383 | -0.167344206 | 6.683978  | 6.683978  |
| 2 | 0.098436913  | -0.081214482 | -1.552083 | -1.552083 |
| 3 | -0.020642333 | -0.107245137 | -1.578296 | -1.578296 |
| 4 | -0.025307141 | -0.211122838 | -1.457079 | -1.457079 |
| 5 | 0.110322062  | -0.095464928 | -2.996066 | -2.996066 |
| 6 | 0.158197604  | -0.088897533 | 0.496085  | 0.496085  |
| 7 | 0.626019667  | -0.078997138 | -1.435241 | -1.435241 |
| 8 | -0.550121437 | -0.15471897  | 6.417764  | 6.417764  |
+---+--------------+--------------+-----------+-----------+