Georg Fuellen

Project Title: E Pluribus Unum: Understanding and Influencing Pluripotency & Reprogramming by Intergrative Bioinformatics

We intend to complete machine learning of pluripotency, now focusing on data mining & integration, based on our PluriNetWork, and associated ExprEssence software that suggests mechanisms involved in pluripotency, by comparing high-throughput datasets. We will expand the PluriNetWork of pluripotency genes/proteins in mouse, and establish it for human (& other species), focusing on transcriptional regulation, signaling & epigenetics. Understanding pluripotency & reprogramming is then based on integrating differential high- throughput datasets into our networks and identifying putative mechanisms, comparing a) different species, b) different data types (protein, RNA, epigenetics, …), and c) different interventions & time series, different states of pluripotency (ICM, Epiblast, iPS, …) & different reprogramming approaches (iPS, SCNT, fusion). We dissect pluripotency & reprogramming in an analysis across all dimensions, using the networks to integrate the data, and to propose intervention schemes (integrating small molecules). The differential analyses by ExprEssence are developed further to cope with these new tasks, incl. components for generating movies, highlighting the startup & shutdown of mechanisms in a network along all dimensions. ExprEssence highlighting will thus identify ensembles of subnetworks to be subjected to detailed modeling, it will support the experimental groups, and it is also the future core of the Bioinformatics Helpdesk for the SPP.

The figure describes putative mechanisms involved in the transition from ES to Epiblast state in mouse, based on data by B. Greber (MPI Münster), see [3] and [4].

References:

[1] Learning biomarkers of pluripotent stem cells in mouse.
Scheubert L, Schmidt R,  Repsilber D, Lustrek M,  Fuellen G.
DNA Res. 2011: accepted for publication.

[2] Proteomic analysis of mouse oocytes reveals 28 candidate factors of the “reprogrammome”.
Pfeiffer MJ, Siatkowski M, Paudel Y, Balbach ST, Baeumer N, Crosetto N, Drexler HC, Fuellen G, Boiani M.
J Proteome Res. 2011 May 6;10(5):2140-53. Epub 2011 Mar 29.

[3] The PluriNetWork: an electronic representation of the network underlying pluripotency in mouse, and its applications.
Som A, Harder C, Greber B, Siatkowski M, Paudel Y, Warsow G, Cap C, Schöler H, Fuellen G.
PLoS One. 2010 Dec 10;5(12):e15165.

[4] ExprEssence–revealing the essence of differential experimental data in the context of an interaction/regulation net-work.
Warsow G, Greber B, Falk SS, Harder C, Siatkowski M, Schordan S, Som A, Endlich N, Schöler H, Repsilber D, Endlich K, Fuellen G.
BMC Syst Biol. 2010 Nov 30;4:164.

[5] Evolution of gene regulation of pluripotency–the case for wiki tracks at genome browsers.
Fuellen G, Struckmann S.
Biol Direct. 2010 Dec 29;5:67.

[6] Evolution of gene regulation–on the road towards computational inferences.
Fuellen G.
Brief Bioinform. 2011 Mar;12(2):122-31.