Intersecting Graph Representation Learning and Cell Profiling

A Novel Approach to Analyzing Complex Biomedical Data


Nima Chamyani

Supervisor: Wesley Schaal

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  • Introduction
  • Aim of the study
  • Methods
  • Results
  • Future outlook
Cell profiling with chemical preturnation
Sample Preparation
Cell Culture
Chemical Perturbation
Fixation
Staining (Painting)
Microscopy
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Graphs
Nodes (Vertices)
Edges (Links)
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Multimodal Graphs
Chemicals
Proteins
Pathways
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Degree of Nodes
Highly connected
Typically connected
Less connected
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Graph's Modules
Community 1
Community 2
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Network Analysis
Community Detection
Centrality Measures
Path Analysis
Subgraph Mining
Graph Clustering
Role Discovery
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Network Analysis (Mathematics)
Community Detection
Centrality Measures
Path Analysis
Subgraph Mining
Graph Clustering
Role Discovery
Graph Representation Learning (ML)
Learning Node Embeddings
Preservation of Graph Structure
Scalability
Edge and Graph-Level Embedding
Incorporation of Node and Edge Attributes
Combination with Deep Learning
Graph Representation Learning (ML)
Learning Node Embeddings
Preservation of Graph Structure
Scalability
Edge and Graph-Level Embedding
Incorporation of Node and Edge Attributes
Combination with Deep Learning
Aim of the Study
Analyzing cell painting biomedical data using graphs.
Enhance understanding of chemical structure-cellular phenotype relationships.
Apply advanced machine learning with graphs in replace to conventional ml techniques.
Developing drug repurposing, drug combination and drug generative models with GRL.
Introducing a new workflow for drug discovery and development.
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Data
BioData Aggregation
BioData Featurization
Graphs
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Data
BioData Aggregation
BioData Featurization
Graphs
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Data
BioData Aggregation
BioData Featurization
Graphs
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Data
BioData Aggregation
BioData Featurization
Graphs
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Graph-Level Molecular Predictor (GLMP)
Bio-Graph Integrative Predictor (BioGIP)
Optimized Molecular Generator (OMG)
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Graph-Level Molecular Predictor (GLMP)
Bio-Graph Integrative Predictor (BioGIP)
Optimized Molecular Generator (OMG)
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Graph-Level Molecular Predictor (GLMP)
Bio-Graph Integrative Predictor (BioGIP)
BioGIP on HeteroGraphs
Optimized Molecular Generator (OMG)
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Graph-Level Molecular Predictor (GLMP)
Bio-Graph Integrative Predictor (BioGIP)
Optimized Molecular Generator (OMG)
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Combination prediction of nodes
Inactive chemicals
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Combination prediction of nodes
Inactive chemicals
Selection should make sense
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Combination prediction of nodes
Inactive chemicals
Selection should make sense
PCA1 Range Selection Method
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Combination prediction of nodes
PCA1 Range Selection Method
Louvain community detection Method
Combination prediction of nodes
PCA1 Range Selection Method
Louvain community detection Method
Combination prediction of nodes
PCA1 Range Selection Method
Louvain community detection Method
Combination prediction of nodes
PCA1 Range Selection Method
Louvain community detection Method
96795-89-0
322473-89-2
eperisone
PIK-75
P7C3
JNJ-38877605
BENZYDAMINE
1257628-77-5
Y 134
67198-19-0
terbinafine
SNAP-94847
Encenicline
BMS-794833
Homochlorcyclizine
1130067-06-9
ML298
JTC-801 free base
lumateperone
drofenine
tolperisone
hydroquinidine
54635-62-0
XANOMELINE
OMG learning from ordinal regression
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OMG learning from ordinal regression
GCPN
GraphAF
Future Perspectives
  • Investigate disparities between regression and classification
  • Validate drug combination discovery approach
  • Examine more network analysis
  • Improve OMG model's components
  • Use graphs for interpretation

Acknowledgements

  • Special thanks to Wes and Ola
  • Sincere appreciation to David, Martin, Anders, Jonne and Phil
  • Gratitude to all master students specially Erik and Victor

Thank You all for listening

InfoGraph

Maximizing the mutual information

Attribute masking

Capturing domain knowledge by learning the regularities of the node/edge attributes distributed over graph structure

GCPN

Graph Convolutional Network (GCN) as a Policy Network: A policy network, in reinforcement learning terms, dictates the action to be taken at each step. Here, the actions are the addition of new nodes and edges to the graph being generated.

Reward Function: This function scores potential actions (i.e., adding a new edge or node) based on their quality.

Optimization with Policy Gradient: GCPN uses a technique called policy gradient to optimize the policy network. The idea is to increase the probability of actions that lead to higher rewards. This is done by iteratively updating the policy network's parameters to maximize the expected cumulative reward.

GraphAF

Autoregressive Approach: The term 'autoregressive' means that the model uses its own previous outputs as input for the next step. For GraphAF, this means generating a new edge in the graph based on the edges that were generated in the previous steps. Essentially, the graph is generated incrementally, with each new edge being influenced by the structure of the graph up to that point.

Flow Model: The 'flow' part of GraphAF refers to the concept of normalizing flows, which is a method used in machine learning to create complex probability distributions. This allows the model to learn a complex distribution over possible graphs, which can then be sampled to generate new graphs.

Sequential Generation: building the graph step by step. At each step, GraphAF proposes a new edge by predicting its two endpoints based on the current graph structure.

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Graphs
Nodes (Vertices)
Edges (Links)
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Multimodal Graphs
Chemicals
Proteins
Pathways
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Degree of Nodes
Highly connected
Typically connected
Less connected
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Graph's Modules
Community 1
Community 2

Jeancarlo C. Leão et. al