Computer model of blood development could speed up search for new leukaemia drugs

Biomedical scientists from the Wellcome Trust-MRC Cambridge Stem Cell Institute and the Cambridge Institute for Medical Research collaborated for the past 2 years with computational biologists at Microsoft Research and Cambridge University’s Department of Biochemistry.  This interdisciplinary team of researchers have developed a computer model to help gain a better understanding of the control mechanisms that keep blood production normal. The details are published today in the journal Nature Biotechnology.

To construct the computer model, PhD student Vicki Moignard from the Stem Cell Institute (Gottgens group) measured the activity of 48 genes in over 3,900 blood progenitor cells that give rise to all other types of blood cell: red and white blood cells, and platelets. These genes include TAL1 and RUNX1, both of which are essential for the development of blood stem cells, and hence to human life.

Computational biology PhD student Steven Woodhouse then used the resulting dataset to construct the computer model of blood cell development, using computational approaches originally developed at Microsoft Research for synthesis of computer code. Importantly, subsequent laboratory experiments validated the accuracy of this new computer model.

Professor Gottgens says: “Because the computer simulations are very fast, we can quickly screen through lots of possibilities to pick the most promising ones as pathways for drug development. The cost of developing a new drug is enormous, and much of this cost comes from new candidate drugs failing late in the drug development process. Our model could significantly reduce the risk of failure, with the potential to make drug discovery faster and cheaper.”

The research was supported by the Medical Research Council, the Biotechnology and Biological Sciences Research Council, Leukaemia and Lymphoma Research, the Leukemia and Lymphoma Society, Microsoft Research and the Wellcome Trust.

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Publication details:

Moignard V, Woodhouse S, Haghverdi L, Lilly AJ, Tanaka Y, Wilkinson AC, Buettner F, Macaulay IC, Jawaid W, Diamanti E, Nishikawa S-I, Piterman N, Kouskoff V, Theis FJ, Fisher J, Gottgens B. Decoding the regulatory network of early blood development from single-cell gene expression measurements. Nature Biotechnology, doi:10.1038/nbt.3154.


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