What is Systems Biology

Transcription

1 What is Systems Biology

2 2 CBS, Department of Systems Biology

3 3 CBS, Department of Systems Biology

4 Data integration In the Big Data era Combine different types of data, describing different things or the same thing with different error City guide analogy: Road maps Arial pictures of buildings Google Maps Street-level pictures Restaurant reviews 4 CBS, Department of Systems Biology

5 Reduction vs Holistic Reductionism seeks to find individual factors that explain/cause a phenomenon Typically study one factor at a time Which cells -> which organelle -> which molecules -> which sites on these molecules -> which atoms and H-bonds involved? Holistic approach looks at many or all components of the system and the interplay between them E.g. map of whole city (as opposed to map of one road) Understanding cancer (requires understanding of many different biological processes) 5 CBS, Department of Systems Biology

6 Increasing Interest in Systems Biology PubMed Term Publications Bioinformatics Systems Biology Cell Cycle Yeast genome completed Nobel Prize for Cell Cycle Human genome completed Year 6 CBS, Department of Systems Biology

7 Also, systems Biology is a top-down science Systems Biology Integration Normal Biology Reducitonist 7 CBS, Department of Systems Biology

8 Systems biology and emerging properties 8 CBS, Department of Systems Biology

9 Integration of whole x-ome to understand life in health and disease genome metabolome LIFE etceterome transcriptome lipidome proteome 9 CBS, Department of Systems Biology

10 10 CBS, Department of Systems Biology

11 From components to models

12 Transcriptional regulation of the Cell Cycle Simon et al. Cell CBS, Department of Systems Biology

13 13 CBS, Department of Systems Biology

14 14 CBS, Department of Systems Biology Tyson JJ, Novak B, J. Theor. Biol. 2001

15 Carbohydrate metabolic map 15 CBS, Department of Systems Biology

16 Mathematical abstraction of biochemistry 16 CBS, Department of Systems Biology

17 The hierarchy of models 17 CBS, Department of Systems Biology

18 The hierarchy of models 18 CBS, Department of Systems Biology

19 From components to models

20 One framework for Systems Biology (part 1) 1. The components. Discover all of the genes in the genome and the subset of genes, proteins, and other small molecules constituting the pathway of interest. If possible, define an initial model of the molecular interactions governing pathway function (how?). 2. Pathway perturbation. Perturb each pathway component through a series of genetic or environmental manipulations. Detect and quantify the corresponding global cellular response to each perturbation. 20 CBS, Department of Systems Biology

21 One framework for Systems Biology (part 2) 3. Model Reconciliation. Integrate the observed mrna and protein responses with the current, pathwayspecific model and with the global network of proteinprotein, protein-dna, and other known physical interactions. 4. Model verification/expansion. Formulate new hypotheses to explain observations not predicted by the model. Design additional perturbation experiments to test these and iteratively repeat steps (2), (3), and (4). 21 CBS, Department of Systems Biology

22 From model to experiment and back again 22 CBS, Department of Systems Biology

23 Systems Biology to address the knowledge/data problem Genome sequencing

24 The human genome sequencing project (HGP) CBS, Department of Systems Biology

25 Sequencing costs over time Drop in costs is faster than Moore s Law (Computer power doubles every 2 years) 25 CBS, Department of Systems Biology

26 Sequencing capability: throughput per machine Kilobases per day per machine 1,000,000, ,000,000 10,000,000 1,000, , ,000 1, Manual slab gel Sanger Chain-termination method 26 CBS, Department of Systems Biology ~3X coverage of a human genome Gel-based systems Automated slab gel Capillary sequencing First-generation capillary Year Human genome Massively parallel sequencing Microwell pyrosequencing Second-generation capillary sequencer 2005 Single molecule? Short-read sequencers 2010 Future

27 Right now, upstairs in DMAC Output: ~30 Gbp/day Human genome is 3.2 Gbp 27 CBS, Department of Systems Biology

28 Completely sequenced genomes by year 28 CBS, Department of Systems Biology

29 Bioinformatics And the wealth of information

30 TCCAAACCCAGGCTCTCTCCCAAACCAGTTTGCGGCAGATGGCCAGTGGAACCTCACTCTCCTCATCAGTAAAAAGGGGGCAGAGTGAGGGTCCTGAGAGCTAGTACAGGGACTGTG TGAAGTAGACAATGCCCAGTGTTTAGCGTAAGAATCAGGGTCCAGCTGGTGCTCCCTAAACAGCAGCTGCTGTTCACTGTTGAAAGGCGCTCTGGAAGGCCAGGCGCGGTGGCTCAT GCTTGTAATCCCAGCACTGTGGGAGGCCGAGGTGGGCGGATCACCTGAGGTAGGGAGTTCGAGACCAGCCTGACCAACGTGGAGAAACCCCATCTCTCCTAAAAATACAAAATTAGC CAGGCGTGGTAGCACATACCTGTAATCCCAGCGACTCGGGAGGCTGAGGCAAGAGAATTGCTTGAAACCAGCAGGGGAGGTTGTGGTGAGCCAAGATCGAGCCATTGCACTCCAGCC AGGGCAACAAGAGGCAAAATGGCGAAACTCCATCTCCGAGAAAAAAAAAAAAAAAGAATACTTTCTGAAAGTATTTATTCATACAAATAAAGACTTGACCCATAAGGTAGGAACGCA AATGGGCCACGGAATCACTCATTCCACAGTATACACCGAGTGCCCTTGAAGTGCTGGGCACTGCTCCAGGATTGGGGGCATATTGGTGAAAAGAGAAGCAAGCCTGCCTGCTCAGAT GGCAGGGAATGGGGAAAAACAGGGAGACAGTTTCCTGTTTGAGATGTTGGGAGTCTGCTTCGAGTAGTATATTTACTGGAAATAGACCACTAACTTGGATGTCCCTTTTTGGAAATG TGCCTGCGTCCAGGGCTGGGTTGGGGCCCCAATGAACTTTGGCTCTGACATAGCTGTTGCCACACTCAGTGGAACTGAATCCATGTTTGCCTTCACCCGGCATCCTTCACCCCAACT CTCCCCGCCACAACATACATCCCATGCCAGCCTGGGGACCCTCAAAGGTGCTTCATCATTAGGTTTGTGGCTGGGTCCTACTGAAGTAAGTCTTGGCACTCAGAGGGATAGGAATTG AATGAAGACATGAGATTCCTCTGCGGGAGGCCTCTCTAGGAAATCTGTGGACTCACACGTTTACTAATGTTGCTGCAGCCCCGCACCCACCTTGGCCTTGGGCAGCCATACTCTAGG GCTTTTGTAACCTCTCCATGTGAGGAACTCAAATTAGACCTGGGTTTGGAGGCGGTGCTCCGAGCTGGCCTTTGGGGGAGGTTTTGTGCGAGGCATTTCCCAAGTGCTGGCAGGATT GTGTCACAGACACAGAGTAAACTTTTGCTGGGCTCCAAGTGACCGCCCATAGTTTATTATAAAGGTGACTGCACCCTGCAGCCACCAGCACTGCCTGGCTCCACGTGCCTCCTGGTC TCAGTATGGCGCTGTCCTGGGTTCTTACAGTCCTGAGCCTCCTACCTCTGCTGGAAGCCCAGATCCCATTGTGTGCCAACCTAGTACCGGTGCCCATCACCAACGCCACCCTGGACC GGGTGAGTGCCTGGGCTAGCCCTGTCCTGAGCACATGGGCAGCTGCCTCCCTTCTCTGGGCTTCCCTTTACCTGCTGGCTGTGGTCGCACCCCCACTCCCAGCTCTGCCTTTTTCTC TTCTGGGTCCCCAGGGTGAAATTCTCACCAGCCCAGGGGACTCTGGAGGCACCCCCTGCCTCCAAACACAGAAGCCTCACTGCAGAGTCCTTCACGGAGGACGGTTCTGTGCTGGGC CTGGAGGGGCTGCCTGGGGGGCAATGACTGATCCTCAGGGTGAGCTCCTGCATGCGCACTGCCCACCAGGGGCCTCATCTCCCCATCTGCAAAATCAGGGAGAGATCTGCCTGAGTC TCCTCCCAGCTGACAGTCAAAGATTCAGCATCAAGCCCCCATCACCAGCTCCCCCCTTCTCCCCAGATCACTGGCAAGTGGTTTTATATCGCATCGGCCTTTCGAAACGAGGAGTAC AATAAGTCGGTTCAGGAGATCCAAGCAACCTTCTTTTACTTTACCCCCAACAAGACAGAGGACACGATCTTTCTCAGAGAGTACCAGACCCGGTGAGAGCCCCCATTCCAATGCACC CCCGATCTCAGCTGTCTGGCCAGAAGACCTGAGCAAGTCCCTCCTTCTTCCTGGCCTTGGCCTTCCCATGGGTGGAACCGGGAGGGTTGGCTTTAATCTCCACCAGAACTCTTGCCC CGGGACTGTGATGGGCGATTGGCCACTTCTCCTCGATAACATTACTGTTTTTCTTCCGCCTTCTGGTTGACTTTAGCCAGAACCAGTGCTTCTATAACTCCAGTTACCTGAATGTCC AGCGGGAGAATGGGACCGTCTCCAGATACGGTGAGGGCCAGCCCTCAGGCAGGAGGGTTCACCGTGGGAACAGGGCAGGCCAGCATAAGGTGGGGGCTGGATGTAGAGCCCTGGAGG CTTTGGGCACAGAGAAATAACCACTAACATTTTTGAGCTCTTACCACGTGCTCAGAAAAAATCCCTAAGAAGACACTGAGAGAATTAGATGAGGAAACATAAGAACAGAGACCTCAA ATAGTTTCCCCAAGGTCACACAGCTTATAATTAGAACTAGAATTGGAACTCCAGGCTGGCTTCAGATCTGCCTCTCTCTCACGCCCTCTTTAAGATCCTTTGCAAACCAATGGTAGA AGCCTGTATGTTGGAGAGGTGGTACCTTCAACTATGTCCCCCATCACCGCAGAGGTGGCACATGGCAGGGATCTGATGGAGCTGAACTGACATCATTTAGCATCCCGAGCCTCCTCT CTGGGCCTCATTTTCCTCCTCTGTAAAACGGGGAGAAAGGCCCTGACAGCCACAGTCTGTGTGAGGCTCCTGAGATCTCATGTACAGAAAGTGCTTGGCGTGGAGCTGGGCACGCAG CAGGGGCTGGGCACACGGTGGCCCAAAGGAGACCCGGGCCTTCACTGATGGGCTTTGTGGCCCCGGACACATTTCTCTTCCAGAGGGAGGCCGAGAACATGTTGCTCACCTGCGTTC CTTAGGGACACCCCTAGGACTCCTCACCTGTAAGACAGGCACCATTGTGCCATCCCATGTTCTCACCCAGAGGCTCTTAAGACCTTGATGTTTGGTTCCTACCTGGACGATGAGAAG AACTGGGGGCTGTCTTTCTATGGTAGGCATGCTTAGCAGCCCCAAACTCATGCCCCTCTCAGGCCTCACCCCCCATTCACCCACCCCTGGGCTGGCCCCTAGAACCCCAGCCCTCCC TGGCCTCCGCCGGGCCCCACCATGTCCCCAGTCAGTCTCCTTGCTCCCCCTGCAGCTGACAAGCCAGAGACGACCAAGGAGCAACTGGGAGAGTTCTACGAAGCTCTCGACTGCTTG TGCATTCCCAGGTCAGATGTCATGTACACCGACTGGAAAAAGGTAAACGCAAGGGATTGGACATTGCCCACCTTGTCCATGGCCCAACTTGGGCAGCCCCAGAGGCCCAGAGCAGGA AAGCTGCCAGGCAAGGCTGCACAGCTAGGCAGATCTTCTGCTTTTAGGCACCTGCCTCACTGTAGGGACAGCTGAGCTCTACAGAGGCCCAGGGGTGGTGGATGAGAGCCCAGGAGG GAGAAGTCCCTGTGAAACCAGGGAGGACCTGAAAGCTAACAGGAGGGAACAGCGTGAGCCACGGGGTTGGGGGATTGGCAATTGGAGGGGACGTAATGCGGGGAGTTACCACCTACA GACGCGTCCCAAACCCCAGGCTTTCACCCCAACCTCCACTCCCCGCTCATTTTTAATACCCGTGCAGTGGGGAATTGATACTGTGGTTTTCAATGTCACCCACACTGCAGCACGGCC ACAGTCACCATCCCGATTTTTGCTACAAATGAAAATTACTGTATAATGAGCTCCTTAACACTTTTCTTTAAACCTGTGTTTGGAAGACTTGTGTTGGTGTGGCCCTGTGCCCTAATA CCTGTGAAATCACAGCACCGATGAGCTGGTTCCAATTTTTAAAATATATACATGCAGTACTTCCATGACTATTCAAAGAAAAACAATTCCTTCCATTTGCCACCTGAGATGACCACC AGGGATGTGAACTACCTCCTGCCCCATCCCCAGCCCCAGGATCCTGGGACAGGGCTTATGAACGCAACCACTGTAGTCAGCTCACTTGATCCACAGCCTGGCACCTCCACTGTCTGG CTAGGGAGCCTCGAATGGGTCCCAAGGCCACCCTGCTCCTCAGTTACATCATCTGCATAGTAGTGGTGGTTGTGAGGAATTCAGGAGCTGCAGCATAAGGGCCCTGCAGGTACTATG TGCTCAGTAAATGCCAGTGGTTCTTAAGGGTCTGAGCTCCCATTGTAGAGGCAAGTAAGCTGAGGTTCAGAGAAGAAAATGACTTGCCCAAGATCACCCAGCTGGGAAGTGACAGTG CCAGGGTTGGAGCCCTGGTTGAGCTGGTTCCACAGGCCAGAGCTCATTCTGCCCTCTCCCCGGAAGACCTCCCACCCTGTCCCCATGCCTCTGCTTCTCCCTCACCCCAATTCCCCG CTGCCTTCTAGGATAAGTGTGAGCCACTGGAGAAGCAGCACGAGAAGGAGAGGAAACAGGAGGAGGGGGAATCCTAGCAGGACACAGCCTTGGATCAGGACAGAGACTTGGGGGCCA TCCTGCCCCTCCAACCCGACATGTGTACCTCAGCTTTTTCCCTCACTTGCATCAATAAAGCTTCGCATCGGCCTTTCGAAACGAGGAGTACAATAAGTCGGTTCAGGAGCCCTCAGG CAGGAGGGTTCACCGTGGGAACAGGGCAGGCCAGCATAAGGTGGGGGCTGGATGTAGAGCCCTGGAGGCTTTGGGCACAGAGGCCACCCTGGACCGGGTGAGTGCCTGGGCTAGCCC TGTCCTGAGCACATGGGCAGCTGCCTCCCTTCTCTGGGCTTCCCTTTACCTGCTGGCTGTGGTCGCACCCCCACTCCCAGCCCCCAACTCTCCCCGCCACAACATACATCCCATGCC 30 CBS, Department of Systems Biology CAGGAGGGTTCACCGTGGGAACAGGGCAGGCCAGCATAAGGTGGGGGCTGGATGTAGAGCCCTGGAGGCTTTGGGCACAGAGGCCACCCTGGACCGGGTGAGTGCCTGGGCTAGCCC

31 31 CBS, Department of Systems Biology Source:

32 32 CBS, Department of Systems Biology

33 Current state-of-the art: Cores - 8 Tb RAM Fastest commercial computer 33 CBS, Department of Systems Biology