StemCellMathLab’18 on tour: Quantitative Analysis of Clonality in Hematopoiesis – Concepts, methods and potentials 

MOTIVATION

The availability of different methods to unambiguously mark individual cells and to follow their clonal progeny over extended time periods provides an unpreceded insight into the organisational principles of many regenerating tissues. Several methods have been established and are continuously enhanced to efficiently label and recover heritable genetic tags in various contexts. As for any new technology, the particular challenges in different experimental situations led to a broad repertoire of specific solutions. For the example of genetic barcoding, different labs use different experimental protocols and analytical tools. As a consequence, the deductions from clonal tracing studies are contingent on both biological and data-analytic assumptions and impose limitations on the comparability of the results. Furthermore, the wealth of available data in clonal tracing studies imposes new challenges on quality control, data management and bioinformatical analysis. Interpreting the data in the focus of a particular experimental question often requires the use of advanced mathematical and computational approaches. Especially the reliable reconstruction of differentiation pathways imposes several analytical and numerical challenges.

The great potential of clonal tracking studies is undeniable. However, these developments need to be accompanied by stringent discussions about the challenges and pitfalls to provide a solid basis of quantitative understanding for the further propagation of these methods. Furthermore, the reconstruction of a clonal development and hierarchical decision processes based on the temporal readouts is conceptually challenging, and it needs to be resolved, which mathematical tools are required and appropriate.

OBJECTIVES

The StemCellMathLab 2018 centres around the questions of how to achieve and make use of quantitative clonal data. It is the aim of the workshop to elucidate both the potentials and the limitations of experimental and computational strategies and to actively foster the discussion between different peer groups in this rapidly developing research field.

SCIENTIFIC THESES/QUESTIONS

A: Understanding haematopoiesis through clonal tracking:

A1: Can we infer the structure and dynamics of haematopoietic differentiation from clonal data? Are there informative theoretical tools to model these processes?

A2: Establishing the core components of the haematopoietic structure – what does it mean to be a “distinct subpopulation” and is this notion useful? How does this structure change throughout development / ageing?

A3: What does the inferred tree mean? Is it a genealogy? Is it the most parsimonious tree? Can we account for intrinsically heterogenous populations?

A4: Can we infer additional information from this data by using different types of mathematical models? e.g. dynamics of haematopoiesis in homeostasis and during stress response, differentiation rates, inference of stem cell/progenitor numbers, asymmetric/symmetric division

B: Clonal competition and clinical applications

B1: How do distinct clones compete and evolve? What is clonal heterogeneity and can we estimate it?

B2: How do mutations affect clonal dynamics – can we follow and model disease modifying mutations?

B3: Can a theoretical understanding of haematopoiesis and the underlying dynamics improve the success of cell and gene therapies?

C: Processing and reporting of clonal data

C1: How should I process my clonal data? How should I report and visualise it?

C2: Should we agree on processing and reporting pipelines?

C3: What remains from your conclusion by the time you take ambiguities in your data into account (e.g. sequencing errors, uniqueness of barcodes, sampling, quantification bias)?

STRUCTURE

Two day workshop with 30 participants.

Presentations should focus directly on the central questions/scientific theses, which will be discussed jointly by the organizers and the participants in advance

Within the workshop, rather short presentations will be complemented with extended time for discussion (i.e. round table style instead of “classical” lecture format).

PROGRAM SCHEDULE

Start:   12th September 2018, 1:00 pm

End:     14th September, 1:00 pm

Please download the detailed schedule here.

CONFIRMED PARTICIPANTS

Name

Affiliation

COSTS AND ACCOMMODATION

We follow the policy that there will be no participation fee for the StemCellMathLab. We will cover accommodation expenses including meals, but we can not pay for travelling costs to/from the workshop.
 

APPLICATION

A limited number of places are now open for external applicants. We particularly encourage the application of junior scientists, i.e. PhD students (preferentially in their final year), post-docs and junior faculty. Applicants should have a background either in clonal studies or in mathematical modeling/systems biology. Furthermore, they should have the vital interest to broaden their scientific view by cross-disciplinary discussions.

If you are interested in participation, please send a short application with CV (including a list of recent publications) and a motivation letter (max. one page) to our administrative support team. 
In the motivation letter, please outline your background and your previous research experience and comment on how you can both contribute and benefit from your workshop participation.

We have (most likely) some funding for travel support available, especially for junior scientists. Please indicate in your motivation letter whether you apply for this fellowship or not.

The application is closed.

WORKSHOP VENUE

The workshop extends over the course of three days (Wednesday, September 12th 2018, 1:00 pm until Friday, September 14th 2018, 1:00 pm) and will be hosted in the Homerton Conference Center in Cambridge, UK

SOCIAL PROGRAM

To be announced

ORGANISATION

This StemCellMathLab is jointly organised by:

• Elisa Laurenti / David Kent (Wellcome Trust/MRC Stem Cell Institute, Cambridge)
• Leïla Perié / Anne Marie Lyne (Quantitative Immuno-hematology, Institut Curie, Paris)
• Ingmar Glauche and Ingo Roeder (Institute for Medical Informatics and Biometry (IMB), Carl Gustav Carus Faculty of Medicine, TU Dresden in cooperation with the Carl Gustav Carus Management GmbH Dresden)

FUNDING