Workshop 3
Targeted treatment of patients through single-cell multi-OMICs Profiling

Organizers
Robert Hänsel-Hertsch - CMMC-Lab. of Genome Biology
Philipp Antczak - CMMC-Lab. of Computational Biology of Aging

Human wellbeing is governed by the individual's (epi)genetic background, their molecular complexity, and their interaction with the environment both internal and external. Heterostasis, which results from a perturbation to one of the many layers of biological organization, can manifest into a disease, such as cancer, or a declining/accelerated health process, such as ageing. These adverse outcomes (AOs) are a focal point in human health research aiming to identify actionable treatments. In most cases the individual's molecular state, however, is not taken into account leading to inefficient drug development and treatment options, as well as higher incidence of side-effects. To ensure that drug development and treatment is as effective as possible, within a given individual, it is imperative to understand the process by which an AO is triggered. This can be achieved by understanding the adverse outcome pathway (AOP) of an AO starting from the molecular initiating event (MIE) and leading through several key events (KEs) across multiple layers of biological information.

MIEs and KEs can also act as actionable drug-targets for precise treatment options. By integrating several AOPs we may identify shared KEs and identify potential new therapies through de novo drug development, drug repurposing or combinations. Importantly, integration of the individual’s molecular to higher level order data, such as ethnicity or genetic background, will provide potential alternative routes by which AOs are caused, allowing for more targeted and effective treatment options.

In this workshop we will explore how cellular composition reflects on disease predisposition, state, and outcome; how multi-OMICs profiling may help in developing AOPs relevant for human diseases, and how we can make use of these frameworks in translational clinical settings. Importantly, we aim to bring a more individualized approach to the identification and treatment of AOs through the use of state-of-the-art single-cell sequencing approaches while integrating these with clinical parameters and ultimately improve patient welfare. 

Interactive Digital Workshop via Zoom Meeting
Robert Hänsel-Hertsch and Philipp Antczak (organizers) are pleased to welcome the on-site workshop participants (see below) and the participants who will join the workshop via Go-To-Meeting.

Participants of the roundtable discussions - digital format:

• Andreas Beyer - CECAD Cologne
• Eric Hahnen - Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology
• Axel Hilmer - Institute for Gernal Pathology and Pathalogical Anatomy
• Julie George - Dept. of Translational Genomics
• Ron Jachimowicz - MPI for Biology of Aging
• Roman-Ulrich Müller - NephroLab Cologne - Kidney Research Center Cologne
• Julian Puppe - Center of Familial Breast and Ovarian Cancer
• Andreas Scheel - Institute for General Pathology and Pathological Anatomy
• Michal-Ruth Schweiger - Institute for Translational Epigenomics
• Armin Tresch - Institute of Medical Statistics and Computational Biology
• Holger Winkels - Clinic III for Internal Medicine

Background information:
A) General publications introducing the topic:

• Eleven grand challenges in single-cell data science. Lähnemann, D. et al. Genome Biol. (2020). doi:10.1186/s13059-020-1926-6.
   
• Single-cell multiomics: technologies and data analysis methods. Lee, J., Hyeon, D. Y. & Hwang, D. Exp. Mol. Med. (2020) 52, 1428–1442.
   
• The role of omics in the application of adverse outcome pathways for chemical risk assessment
  Brockmeier EK, Hodges G, Hutchinson TH, Butler E, Hecker M, Tollefsen KE, Garcia-Reyero N, Kille P, Becker D, Chipman K, Colbourne J, Collette TW, Cossins A, Cronin M, Graystock P, Gutsell S, Knapen D, Katsiadaki I, Lange A, Marshall S, Owen SF, Perkins EJ, Plaistow S, Schroeder A, Taylor D, Viant M, Ankley G, Falciani F. Toxicol Sci. 2017 Aug 1;158(2):252-262. doi: 10.1093/toxsci/kfx097 - https://academic.oup.com/toxsci/article/158/2/252/3835520

B) Interesting publications of the organizers

• Landscape of G-quadruplex DNA structural regions in breast cancer.
  Hänsel-Hertsch R, Simeone A, Shea A, Hui WW, Zyner KG, Marsico G, Rueda OM, Bruna A, Martin A, Zhang X, Adhikari S, Tannahill D, Caldas C & Balasubramanian S (2020) Landscape of G-quadruplex DNA structural regions in breast cancer. Nat. Genet. 52:878-883 - https://www.nature.com/articles/s41588-020-0672-8
   
• DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential.
  Hänsel-Hertsch R, Antonio M Di and Balasubramanian S (2017) DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential. Nat. Rev. Mol. Cell Biol. 18: 279–284 - https://www.nature.com/articles/nrm.2017.3
   
• G-quadruplex structures mark human regulatory chromatin.
  Hänsel-Hertsch R, Beraldi D, Lensing S V, Marsico G, Zyner K, Parry A, Di Antonio M, Pike J, Kimura H, Narita M, Tannahill D & Balasubramanian S (2016) G-quadruplex structures mark human regulatory chromatin. Nat. Genet. 48: 1267–72 - https://www.nature.com/articles/ng.3662
   
• Chemical hazard prediction and hypothesis testing using quantitative adverse outcome pathways.
  Perkins, E J, Gayen K, Shoemaker J E, Antczak P, Burgoon L, Falciani F, Gutsell S, Hodges G, Kienzler A, Knapen D, McBride M, Willett C, Doyle F J and Garcia-Reyero N (2019) Altex 36(1):91–102. - https://www.altex.org/index.php/altex/article/view/1160