Suchergebnisse

This work was funded by the BLUEPRINT project (European Union's Seventh Framework Programme grant 282510), the NIHR Cambridge Biomedical Research Centre, and the Austrian Academy of Sciences. F.A.C. is supported by a Medical Research Council Clinical Training Fellowship (grant MR/K024043/1). F.H. is supported by a postdoctoral fellowship of the German Research Council (DFG; grant HA 7723/1-1). J.K. is supported by a DOC Fellowship of the Austrian Academy of Sciences. W.H.O. is supported by the NIHR, BHF (grants PG-0310-1002 and RG/09/12/28096), and NHS Blood and Transplant. E.L. is supported by a Wellcome Trust Sir Henry Dale Fellowship (grant 107630/Z/15/Z) and core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. M. Frontini is supported by the BHF Cambridge Centre of Excellence (grant RE/13/6/30180). C.B. is supported by a New Frontiers Group award of the Austrian Academy of Sciences and by a European Research Council (ERC) Starting Grant (European Union's Horizon 2020 research and innovation program; grant 679146). Supplement

Hematopoietic stem cells give rise to all blood cells in a differentiation process that involves widespread epigenome remodeling. Here we present genome-wide reference maps of the associated DNA methylation dynamics. We used a meta-epigenomic approach that combines DNA methylation profiles across many small pools of cells and performed single-cell methylome sequencing to assess cell-to-cell heterogeneity. The resulting dataset identified characteristic differences between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral blood. We also observed lineage-specific DNA methylation between myeloid and lymphoid progenitors, characterized immature multi-lymphoid progenitors, and detected progressive DNA methylation differences in maturing megakaryocytes. We linked these patterns to gene expression, histone modifications, and chromatin accessibility, and we used machine learning to derive a model of human hematopoietic differentiation directly from DNA methylation data. Our results contribute to a better understanding of human hematopoietic stem cell differentiation and provide a framework for studying blood-linked diseases. ; This work was funded by the BLUEPRINT project (European Union's Seventh Framework Programme grant 282510), the NIHR Cambridge Biomedical Research Centre, and the Austrian Academy of Sciences. F.A.C. is supported by a Medical Research Council Clinical Training Fellowship (grant MR/K024043/1). F.H. is supported by a postdoctoral fellowship of the German Research Council (DFG; grant HA 7723/1-1). J.K. is supported by a DOC Fellowship of the Austrian Academy of Sciences. W.H.O. is supported by the NIHR, BHF (grants PG-0310-1002 and RG/09/12/28096), and NHS Blood and Transplant. E.L. is supported by a Wellcome Trust Sir Henry Dale Fellowship (grant 107630/Z/15/Z) and core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute. M. Frontini is supported by the BHF Cambridge Centre of Excellence (grant RE/13/6/30180). C.B. is supported by a New Frontiers Group award of the Austrian Academy of Sciences and by a European Research Council (ERC) Starting Grant (European Union's Horizon 2020 research and innovation program; grant 679146).

Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin.

Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin.