A presentation at Presentation about my Master Thesis in in Darmstadt, Germany by Luis Vls
The Role of Machine Learning and Cell-Painting in Drug Development 09.09.2020 | Fachbereich Chemie | Luis Vollmers | Master Thesis | University of Cambridge 1
What is Cell Painting? What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 2
What is Cell Painting? What is Cell Painting? What is ML? How to use ML and CP? Why is that relevant? Questions? vs. 09.09.2020 | Fachbereich Chemie | Luis Vollmers | Master Thesis | University of Cambridge 3
Treatment, Staining and Plating What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 4
High-Throughput-Imaging What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 5
Automated Analysis of the Cell Images What is Cell Painting? What is ML? How to use ML and CP? Why is that relevant? Questions? • CellProfiler • Recognizes Cells • Recognizes Organelles • Generates Numerical Data • Downstream Data Analysis (ML) 09.09.2020 | Fachbereich Chemie | Luis Vollmers | Master Thesis | University of Cambridge 6
Data Set Used in My Master Thesis What is Cell Painting? What is ML? How to use ML and CP? Why is that relevant? Questions? • ~1800 features extracted by CellProfiler • Features are AreaOfNucleus, ERGranularity, CellRoundness, etc… • ~30000 distinct compounds • The total data set comprises ~54000000 entries • No human could ever comprehend so much information • Machine Learning (ML) Methods can use high-dimensional Information 09.09.2020 | Fachbereich Chemie | Luis Vollmers | Master Thesis | University of Cambridge 7
What is Machine Learning? What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 8
Traditional Programming: a.k.a. Software 1.0 What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 9
Traditional Programming: a.k.a. Software 1.0 What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 10
What Software 1.0 is really bad at What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 11
Machine Learning: a.k.a. Software 2.0 What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 12
Different Machine Learning Models What is Cell Painting? What is ML? How to use ML and CP? Random Forest Classifier Why is that relevant? Questions? Support Vector Machines Neural Networks 09.09.2020 | Fachbereich Chemie | Luis Vollmers | Master Thesis | University of Cambridge 13
The Simplest Deep Neural Network What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 14
The Simplest Deep Neural Network What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 15
Calculating the Hidden Layer: h What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 16
Calculating the Output: y What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 17
How to Combine CP and ML? What is Cell Painting? What is ML? How to use ML and CP? Why is that relevant? Questions? What would be the target? 09.09.2020 | Fachbereich Chemie | Luis Vollmers | Master Thesis | University of Cambridge 18
Toxicity Endpoints are Key What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 19
Open Source Toxicity Databases (DB) What is Cell Painting? What is ML? How to use ML and CP? Why is that relevant? Questions? • Examples for Open Source DB • DILIrank – Livertoxicity • DrugBank – Complex Encyclopedia with various Endpoints • EcoTox – Data on Ecological Toxicity • SIDER – Side Effects Data Base (Adverse Drug Reactions) • PubChem - Complex Encyclopedia with various Endpoints • Handling of Data bases is not trivial • Size, accessibility and complexity of the stored information • Data needs to be understood before it can be used in a model 09.09.2020 | Fachbereich Chemie | Luis Vollmers | Master Thesis | University of Cambridge 20
Why is Toxicity Prediction from CP beneficial? What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 21
Thank you for your attention! Feel free to ask questions. What is Cell Painting? 09.09.2020 | Fachbereich Chemie | What is ML? Luis Vollmers How to use ML and CP? | Master Thesis | Why is that relevant? University of Cambridge Questions? 22
‘The Role of Machine Learning and Cell-Painting in Drug Development’ was the opening presentation for my master thesis supervised by the TU Darmstadt and the University of Cambridge. The project was embedded in computational biochemistry and data science whilst the Darmstadt group did experimental research. Therefore the aim of this presentation was to introduce the work group in Darmstadt to the necessary research and the methods used. Hence, methods like machine learning, cell painting and what can hopefully be achieved by combining the two is briefly outlined which means that the presentation is suitable for scientists who are not experts on the topic.
The following resources were mentioned during the presentation or are useful additional information.
Dr. Andreas Bender was my supervisor at the University of Cambridge during the time I gave that presentation.
Prof. Dr. Schmitz was my supervisor at the Technische Universitaet Darmstadt during the time I gave that presentation.
Picture made by Thomas Shafee
Image made by Recursion Pharmaceuticals
Image made by angellodeco | Fotolia
Figure made by Broad Institute
Logo of CellProfiler-Software
Image made by CJ Haughey
Picture made by Emilie Bess
Schema made by Embention
Picture made by May Lee
Original publication, for a large phenotypic profiling assay, released from Broad Institute. This paper explains the experimental methods used to undertake the assay and the purpose and possible applications of this rather large data set. It is a very detailed paper for very interested readers with a large methods section that gives every information needed to replicate the results.
This publication discusses a cell painting assay released from Broad Institute. It is a brief summary of how the image data is first obtained experimentally, a list of the fluorescent dyes is given and afterwards the CellProfiler Software is referenced for being the tool to derive numerical features with. A short overview over potential uses is also given.
A phenotypic screening assay for glucocorticoid receptors is here repurposed to predict protein activity in seemingly unrelated assays. From this assay they built a machine learning model, helped increase their drug target hit rates by up to 250 times in experiment.
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