NDLI: Logical modelling of haematopoietic cell fate reprogramming

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Logical modelling of haematopoietic cell fate reprogramming

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Logical modelling of haematopoietic cell fate reprogramming

Content Provider	ACM Digital Library
Author	Thieffry, Denis
Abstract	Logical modelling constitutes a flexible framework to build qualitative predictive models, which can be readily analysed or simulated as such, and potentially used as scaffolds to build more quantitative (continuous or stochastic) models. We use Multi-valued Decision Diagrams to implement (multi-level) logical updating rules in the modelling software GINsim [2]. This representation enabled the development of efficient algorithms for the identification of stable states, or yet to identify specific (positive or negative) regulatory circuits involved in specific dynamical properties (e.g., multiple attractors or sustained oscillations). To cope with larger molecular networks, we have implemented a flexible reduction method conserving the attractors of the original model into our software GINsim [4]. Furthermore, we have delineated an incremental, compositional strategy to build large models by combining logical models for simpler regulatory modules. These methodological developments have been recently applied to the differentiation of T-helper cells into different subtypes, depending on activation by antigen presenting cells and on micro-environment (combinations of cytokines) [3]. In my lecture, I will introduce the biological background and generic questions regarding the organisation and function of the signalling/regulatory circuits underlying cell fate decision. I will illustrate the types of insights gained by logical modelling through an application dealing with blood cell differentiation and developed in collaboration with Thomas Graf (Center for Genomic Regulation, Barcelona, Spain) [1]. More specifically, I will present a model recapitulating the differentiation of common lymphocyte/myoloid progenitors into T and B lymphocyte committed progenitors in the presence of proper lymphokine signalling. Furthermore, this model enables the reproduction of T or B lymphocyte precursors into macrophages upon induced expression of the transcription factors CEBPa or CEBPb, in the presence of specific lymphokines. Finally, this model can be used to simulate the behaviour of the system in novel situations, e.g. in the presence of combinations of perturbations such as gene knockouts or ectopic expressions.
Starting Page	7
Ending Page	7
Page Count	1
File Format	PDF
ISBN	9781450308175
DOI	10.1145/2037509.2037512
Language	English
Publisher	Association for Computing Machinery (ACM)
Publisher Date	2011-09-21
Publisher Place	New York
Access Restriction	Subscribed
Content Type	Text
Resource Type	Article

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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