Subarea 5: Computational and Systems Biology of Aging

Subarea 5 focuses on the development of methods to analyse and understand complex biological systems. This work includes the design of computer algorithms and biostatistical approaches as well as the development of novel Omic strategies (i.e. genomics/epigenomics, transcriptomics, proteomics, and metabolomics) to study aging and aging-related diseases. According to the FLI, due to the Subarea's expertise in computational data analysis, it is deeply interconnected with all other Subareas. The Subarea hosts two critical core facilities (Life Science Computing, Proteomics) and provides consulting services in statistics. Furthermore, it organizes courses on data analysis and statistics.

The research is defined by five focus areas:

Mapping extrinsic and intrinsic factors influencing stem cells during aging,
Integration of spatiotemporal proteomics and transcriptomics data,
Comprehensive evaluation of qualitative and quantitative expression changes,
Identification and analysis of epigenomic alterations during aging and age-related diseases, and
Network analysis of genomic, transcriptomic and epigenomic alterations during aging.

Research focus of Subarea 5.

The biology of aging can be viewed as a multilayered array of networks at the level of organs, cells, molecules, and genes. The FLI wants to meet this complexity by establishing the new Subarea on “Computational and Systems Biology of Aging”. The overall goal is to interconnect research at different scales, taking place in Subareas 1-4 of the Institute’s research program. The new group on Systems Biology will integrate data from networks at multiple scales and will thus point to mechanisms and interactions that would not be seen in unilayer approaches.

Publications

(since 2016)

2017

Proteomic Analysis Reveals GMP Synthetase as p53 Repression Target in Liver Cancer.
Holzer K, Drucker E, Roessler S, Dauch D, Heinzmann F, Waldburger N, Eiteneuer EM, Herpel E, Breuhahn K, Zender L, Schirmacher P, Ori A, Singer S
Am J Pathol 2017, 187(2), 228-35
Semantic biomarker selection for functional genomics of heart failure model organisms
Lausser L, Just S, Rottbauer W, Kestler HA
In: 2017 Computing in Cardiology (CinC), Rennes,France 2017 2017, 1-4, IEEE Publications, Los Alam
Generalized enhanced suffix array construction in external memory.
Louza FA, Telles GP, Hoffmann S, Ciferri CDA
Algorithms Mol Biol 2017, 12, 26
Landscape of nuclear transport receptor cargo specificity.
Mackmull MT, Klaus B, Heinze I, Chokkalingam M, Beyer A, Russell RB, Ori** A, Beck** M
Mol Syst Biol 2017, 13(12), 962 ** co-corresponding authors, highlighted in the “Principle of Systems Biology” - Cell Systems 6 - 2018
Telomerase abrogates aneuploidy-induced telomere replication stress, senescence and cell depletion.
Meena JK, Cerutti A, Beichler C, Morita Y, Bruhn C, Kumar M, Kraus JM, Speicher MR, Wang ZQ, Kestler HA, Fagagna Fdd, Günes C, Rudolph KL
EMBO J 2017, 36(19), 2922-4 Erratum for EMBO J 2015 volume 34 page 1371
ViSiBooL - visualization and simulation of Boolean networks with temporal constraints.
Schwab J, Burkovski A, Siegle L, Müssel** C, Kestler** HA
Bioinformatics 2017, 33(4), 601-4 ** co-senior authors
An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.
Scott RA, Scott LJ, Mägi R, Marullo L, Gaulton KJ, Kaakinen M, Pervjakova N, Pers TH, Johnson AD, Eicher JD, Jackson AU, Ferreira T, Lee Y, Ma C, Steinthorsdottir V, Thorleifsson G, Qi L, Van Zuydam NR, Mahajan A, Chen H, Almgren P, Voight BF, Grallert H, Müller-Nurasyid M, Ried JS, Rayner WN, Robertson N, Karssen LC, van Leeuwen EM, Willems SM, Fuchsberger C, Kwan P, Teslovich TM, Chanda P, Li M, Lu Y, Dina C, Thuillier D, Yengo L, Jiang L, Sparso T, Kestler HA, Chheda H, Eisele L, Gustafsson S, Frånberg M, Strawbridge RJ, Benediktsson R, Hreidarsson AB, Kong A, Sigurðsson G, Kerrison ND, Luan J, Liang L, Meitinger T, Roden M, Thorand B, Esko T, Mihailov E, Fox C, Liu CT, Rybin D, Isomaa B, Lyssenko V, Tuomi T, Couper DJ, Pankow JS, Grarup N, Have CT, Jørgensen ME, Jørgensen T, Linneberg A, Cornelis MC, van Dam RM, Hunter DJ, Kraft P, Sun Q, Edkins S, Owen KR, Perry JR, Wood AR, Zeggini E, Tajes-Fernandes J, Abecasis GR, Bonnycastle LL, Chines PS, Stringham HM, Koistinen HA, Kinnunen L, Sennblad B, Mühleisen TW, Nöthen MM, Pechlivanis S, Baldassarre D, Gertow K, Humphries SE, Tremoli E, Klopp N, Meyer J, Steinbach G, Wennauer R, Eriksson JG, Mӓnnistö S, Peltonen L, Tikkanen E, Charpentier G, Eury E, Lobbens S, Gigante B, Leander K, McLeod O, Bottinger EP, Gottesman O, Ruderfer D, Blüher M, Kovacs P, Tonjes A, Maruthur NM, Scapoli C, Erbel R, Jöckel KH, Moebus S, de Faire U, Hamsten A, Stumvoll M, Deloukas P, Donnelly PJ, Frayling TM, Hattersley AT, Ripatti S, Salomaa V, Pedersen NL, Boehm BO, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, Hansen T, Pedersen O, Barroso I, Lannfelt L, Ingelsson E, Lind L, Lindgren CM, Cauchi S, Froguel P, Loos RJ, Balkau B, Boeing H, Franks PW, Gurrea AB, Palli D, van der Schouw YT, Altshuler D, Groop LC, Langenberg C, Wareham NJ, Sijbrands E, van Duijn CM, Florez JC, Meigs JB, Boerwinkle E, Gieger C, Strauch K, Metspalu A, Morris AD, Palmer CN, Hu FB, Thorsteinsdottir U, Stefansson K, Dupuis J, Morris AP, Boehnke M, McCarthy MI, Prokopenko I, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
Diabetes 2017, 66(11), 2888-902
Wnt activity and basal niche position sensitize intestinal stem and progenitor cells to DNA damage.
Tao S, Tang D, Morita Y, Sperka T, Omrani O, Lechel A, Sakk V, Kraus J, Kestler HA, Kühl M, Rudolph KL
EMBO J 2017, 36(19), 2920-1 Erratum for EMBO J 2015 volume 34 page 624

2016

Boolean modeling identifies greatwall/MASTL as an important regulator in the AURKA network of neuroblastoma.
Dahlhaus M, Burkovski A, Hertwig F, Mussel C, Volland R, Fischer M, Debatin KM, Kestler** HA, Beltinger** C
Cancer Lett 2016, 371(1), 79-89 ** co-corresponding authors
Automated structure modeling of large protein assemblies using crosslinks as distance restraints.
Ferber M, Kosinski J, Ori A, Rashid UJ, Moreno-Morcillo M, Simon B, Bouvier G, Batista PR, Müller CW, Beck M, Nilges M
Nat Methods 2016, 13(6), 515-20 published during change of institution