Topic 6 | Pathways and Signalling

Class Details

📅 Date: 13/14 October 2025
📖 Synopsis: Exploring databases: KEGG, Reactome

Lecture topics

• Exploring EGFR signalling pathways — KEGG
• Mapping growth factor–mediated cascades — Reactome
• Comparing complementary pathway visualisations — KEGG / Reactome

Learning goals

• Learn to navigate pathway maps to locate molecular participants in signalling.
• Compare representations of EGFR signalling across pathway databases.
• Connect EGFR pathways to therapeutic strategies such as tyrosine kinase inhibition in cancer treatment.

Theory

About Reactome and KEGG

Reactome and KEGG are major pathway databases that help us understand how genes and proteins work together in biological systems.

• Reactome focuses on detailed, expert-curated biological pathways, showing how molecules interact in signaling, metabolism, and disease processes. Each step in a pathway is supported by scientific evidence and linked to external resources such as UniProt and PubMed.

• KEGG (Kyoto Encyclopedia of Genes and Genomes) provides a more schematic view of pathways, connecting genes, proteins, metabolites, and drugs across species. It is especially strong in illustrating metabolic and signaling networks and linking them to human diseases and therapeutic compounds.

In the context of the pharmaceutical sciences, these databases are essential resources because they show how molecular targets (like receptors or enzymes) fit into larger cellular processes and disease mechanisms.

They complement other databases such as DrugBank (focused on drugs and their targets), UniProt (focused on proteins), and Ensembl, ClinVar or OMIM (focused on genes, their variants, and phenotypes/diseases).

Together, they provide a complete view from gene → protein → pathway → drug → therapy, enabling a systems-level understanding of how medicines work and how resistance or side effects may arise.

Practical

TP Activity 6

EGFR Signalling & Targeted Therapies

Goal

By the end of this activity, you should be able to:

• Explore and critically interpret bioinformatics databases to connect the drug target EGFR gene with its cellular functions, pathway interactions, and drugs that act on it.

• Use the following databases:

  • KEGG
  • Reactome

How to Work

1. Search for “Epidermal Growth Factor Receptor” (EGFR) in DrugBank.

   Note: Make sure to search under the Targets section - not under Drugs (which is the default).

   In the DrugBank entry, answer the following:

   • 1.1. How many drugs are currently reported in DrugBank to interact with EGFR?

   • 1.2. How many of these are inhibitors?

   • 1.3. How many drugs are experimental?

2. Find and follow the UniProt external link from the DrugBank page. Briefly explore the UniProt entry for EGFR.

   In UniProt, answer the following:

   • 2.1. What is the UniProt ID for the protein? How long is the protein?

   • 2.2. Is this a well-annotated and reliable entry?

     • (Hint: check the annotation score and click the info icon to understand what it represents. )

   • 2.3. In the Genomic coordinates section, on which chromosome and strand is the EGFR gene located? Which genome assembly version is used?

   • 2.4. What is the genomic location and how many exons does the canonical isoform have?

3. In UniProt, go to the External links tab and find the section Enzyme and Pathway Databases. There you will find several Reactome pathway links involving EGFR.

   Follow the link to the pathway “Signaling by EGFR.” Explore the pathway and answer the following:

   • 3.1. Write a brief (1-sentence) summary of the EGFR function.

   • 3.2. How many molecules (chemical compounds and proteins) are involved in the pathway?

     • (Hint: Look in the Molecules tab.)

   • 3.3. Which gene/protein shows the highest expression across tissues and organs?

     • (Hint: Look in the Expression tab. The rows of the heatmap are gene names.)

   • 3.4. Download the pathway diagram as a high-resolution PNG file.

     • (Hint: Look in the Downloads tab for Pathway Diagram.)

   • 3.5. Save an image of the EGFR signaling illustration.

     • (Hint: There is no menu for this. You must select the ilustration, click on it with your mouse, and choose Save Image as… .)

   • 3.6. Find and explore the Voronoi visualization (Reactfoam) of the complete Reactome pathways. Download the image.

     • (Hint: Navigate to the Show all screen, and at the top, click the circle that looks like a pattern of bubbles pressed tightly together and download the image with the dedicated button.)

4. Return to the UniProt entry and locate the KEGG link under the section Genome Annotation Databases.

   In KEGG, answer the following:

   • 4.1. How many OMIM entries are linked from the EGFR gene page? What are the OMIM entries about (page name).

   • 4.2. Explore the pathway “EGFR Tyrosine Kinase Inhibitor Resistance.” Identify the name of the drugs marked as tyrosine kinase inhibitors in this pathway.

   • 4.3. Are these drugs also listed in the DrugBank entry for EGFR target?

     • What might explain any discrepancy between the number of drugs listed in DrugBank (answer to question 1.1) and the number of drugs listed in KEGG?