Interactions

Explore the interactions between ligands and proteins. This is the main navigator to the chemoproteomics data, containing profiles for 407 fragments. The app also showcases competition assays for a few selected fragments

Protein-sets

Input a set of proteins and see how many fragments interact with them according to our chemoproteomics data. We categorize proteins by their promiscuity/specificity levels to easily detect reported effect such as labeling bias

Enrichment Analysis

Explore fragment profiles from an enrichment perspective. We capture protein annotations of multiple scopes, from domains and families to molecular functions and cellular localization. We offer global and detailed views for each fragment

Fragment Predictor

Predict whether your fully-functionalized fragment of interest is likely to be promiscuous or associated with a specific interactome signature. We have predefined 10 interactome signatures capturing high-level biological processes that emerged from our chemoproteomics data

On-the-fly Model

Build a machine learning model on the fly to predict potential interactions between your fully-functionalized fragments and proteins of interest. Sets of proteins are accepted and organized in coherent subsets to maximize the chance of obtaining a good model

FAQ

Do i have to clear existing text to search for a new Protein in interactions app?

NO. To change selected protein, there is no need to select whole existing term or delete or type new. Just place the mouse cursor in the search box and just start to type new protein! Old text is automatically cleared


I did not find my Protein/Gene (example, DDB1) of interest in search box in interactions app.

Names like caspase or ddb1 appear many times in description of proteins, therefore search engine is not able to pick the correct one. Type specific input such as DNA damage-binding protein 1 or DDB1 DNA dama.. to find DDB1. Search with UniProt Accession (Q16531 for DDB1) is better !


My fragment of interest (example C008) is not displayed in the Gen1 search box in interactions app.

Gen1 Fragment selection menu is dynamically updated based on the selected Protein and threshold filters applied. If you are interested in a specific Gen1 Fragment, then clear all filters, i.e., select 'no filter' option for P values, adjusted P values and filterSet (fS) and/or select a promiscuous Protein such as TOMM22


Why changing the threshold for P values, adjusted P values and filterSet (fS) does not change the plot in interactions app ?

That is correct. Plots are static. They are not dynamically updated based on threshold values. Changing the threshold for P values, adjusted P values and filterSet (fS) only updates the Table. Pre- set (i.e. default) filterSet (fS or fS2) were used to create plots


Can i change the order of Gen1 Fragments displayed in the search box menu in interactions app?

Order of Fragments displayed in search menu matches the original order in the Table. Re-adjusting the table, for example: sort the table based on Foldchange (Fc) values or number of Protein/Fragment hits will not change the order of the Fragments in the search menu

Changing the threhold for P values, adjusted P values and filterSet (fS) updates the original Table, consequently results in a change in the order of Gen1 Fragment displayed in search menu


What was the criteria to label a Protien or Fragment as Promiscuous ?

10% hit/regulated ratio for Proteins and 5% for Fragments


Explain Promiscuity and Ontology Prediction models

  • We built two types of Promiscuity models A. Global (3) and B. Specific (9)
  • And we built Ontology (10) models.
  • Area Under Receiver Operating Characteristic (AUROC) of > 0.75 is considered a good model
Global number of Proteins AUROC
Prom-0 100+ 0.818
Prom-1 200+ 0.800
Prom-2 300+ 0.713
Specific number of Proteins number of Fragments AUROC
Prom-0-0 5+ < 4 0.818
Prom-0-1 10+ 4 - 40 0.809
Prom-0-2 50+ > 40 0.857
Prom-1-0 10+ < 4 0.771
Prom-1-1 15+ 4 - 40 0.855
Prom-1-2 100+ > 40 0.858
Prom-2-0 50+ < 4 0.771
Prom-2-1 100+ 4 - 40 0.743
Prom-2-2 200+ > 40 0.814
Signature Models Ontology AUROC
Sign-0 Endoplasmic reticulum 0.872
Sign-1 RNA binding 0.727
Sign-2 Lysosome 0.938
Sign-3 Proteasome complex 0.616
Sign-4 Mitochondria 0.519
Sign-5 Nucleous 0.702
Sign-6 Transmembrane transporter 0.756
Sign-7 Microtubule 0.557
Sign-8 Organic acid binding 0.706
Sign-9 Envelope 0.806

Cite

Offensperger et al., Science (2024)

Contact

Georg Winter's group at CeMM