Dissertation Research Notes

Dissertation Research Notes

November21, 2006 Glenn Booker

Key Dissertation Elements

Physiome Issues

Critters

Hierarchy of Multi-scale Modeling

Projects, Organizations, Markup Languages & Ontologies

Vocabulary

Major Aging Theories

Papers

Books

Key Dissertation Elements

Modeling of aging versus normal adult. Robustness, and its influence on the aging process?
Physiome project, multiscale modeling, markup languages.
Key players include Denis Noble (heart model, retired in 2004), some guy from Stanford, and Peter Hunter (NZ organizer of the physiome)
Informatics backbone, and its connection to multiscale modeling

Physiome Issues

Spatial scales range from nm distance (e.g. diameter of an ion channel) to the meter-scale size of an adult human, for a factor of 10^9.
Temporal scales range from microsecond events (Brownian motion) to a billion seconds in a lifespan, for a factor of 10^15.
As a result, computation of a solution is often a stiff problem, and may require several levels of complexity of models (less complex when that’s accurate enough, more complex when required)
Making transition between stochastic(state transition, Monte Carlo) and continuum models
Making transition among 3-D, 2-D, and 1-D models
Structure and function are heavily intertwined in biology (unlike good software!)
Connecting the genome, proteome, morphome (organism structure, and includes aging effects), and physiome (Bassingthwaighte, 2000)
Knowing applicability and limits of models across various conditions, species, etc.
This isn’t just for humans!
What happens when the valid scope of a model is exceeded?

Critters

Common
Name / Latin / Genes / Notes
Amoeba / Dictyostelium discoideum / Also called a slime mold?
Bacterium / Escherichia coli / 3,600 / Sequenced by genome project.
Fly, Fruit / Drosophilia melanogaster
Human / Homo sapiens sapiens
Mouse, lab / Mus musculus
Nematode / Caenorhabditis elegans / 19,536 / 959 cells, all genetically identical
Rat, Norway / Rattus norvegicus / Some data at GAN.
Yeast, Baker’s / Saccharomyces cerevisiae / 6,000 / Sequenced here.

Hierarchy of Multi-scale Modeling

Partly from (Hunter, 2004 Hunter, 2005).

Structure / Function
Culture
Race? Ethnicity?
Society / Civilization?
Family / Social unit?
Person – is this the highest level we’re concerned with?
Organ systems – 11 or 12 systems; Circulatory, respiratory, musculo-skeletal, integument, digestive, CNS, endocrine, lyphatic, male & female reproductive, and special sense organs.
Organ – 50 organs
[No, no organ recital here.]
Tissue– four majortypes; muscle, nerve, connective, and epithelial / Movement, comm., structure, protection
Cell – 200-300 cell types, in 17 categories; blood, bone, cardiac, cartilage, CNS, epidermal, gastrointestinal, immune, neural, liver, pancreatic, respiratory, sensory system, skeletal muscle, generic, and male female reproductive cells. / Cell function
Organelle – 9 common ones, plus specialized types (e.g. muscle’s sarcoplasmic reticulum). Common organelles are: cell membrane, mitochondria, nucleus, endoplasmic reticulum, Golgi apparatus, centrioles, ribosomes, lysosomes and peroxisomes.
Proteins (100,000), lipids, carbohydrates + DNA = cell components
Nine families of proteins: gene regulation proteins, structural proteins, receptor proteins, signalling proteins, transport proteins, motor proteins, enzymatic proteins, storage proteins and defensive proteins. / Called “Systems biology” from here down.
Translation, protein folding, post-translation modification
Transcription, gene regulation, post-transcription modification
Genes – 19,000 to 35,000 of them; where do SNPs fit in?
DNA – 3.2 billion base pairs / More for females?

Projects, Organizations, Markup Languages & Ontologies

Project or
Organization / Description
AnatML / Anatomy muscular/skeletal markup language, supposedly developed in NZ (links dead as of 8/17/06).Has link at Physiome page, but is still dead as of 9/21/06.
BASIS / Biology of ageing e-science integration and simulation system, formed in 2002.
CellML / The purpose of CellML is to store and exchange computer-based mathematical models. Has an API.
FieldML / Part of physiome project, FieldML is an XML-based language for describing time-varying and spatially-varying fields.
GAN / Gene Aging Nexus (GAN) is a data mining platform for the biogerontological-geriatric research community. Hosted at USC.
Gene Ontology Consortium / “…provides a controlled vocabulary to describe gene and gene product attributes in any organism”
GO / Gene Ontology,
GOBO / Global Open Biological Ontologies, now Open Biomedical Ontologies.
Human Genome / During 1990-2003, it mapped the human genome from 5 individuals.
IEEE-EMBS / IEEE Engineering in Medicine and Biology Society
IUPS / International Union of Physiological Sciences, sponsor of Physiome project.
Lung Atlas Project / PI at U of Iowa is Joseph Reinhardt. B Li published on this in 2003 – see (Crampin, 2004a)
MAF / Multimodal Application Framework,
MAGE-ML / MAGE-ML aims to provide a standard for the representation of microarray expression data.
MathML / MathML is a low-level specification for describing mathematics as a basis for machine to machine communication. From W3C.
Metagraph / “The MetaGraph Framework is designed to solve problems encountered when managing multiple hypotheses of changing biological information associated with experimental data.” Last updated 2003?
OME / Open Microscopy Environment,
OWL / Ontology web language,
PathwayML?
Physiome / The Physiome Project is a worldwide public domain effort to provide a computational framework for understanding human and other eukaryotic physiology. See also
PhysioML / XML for physiological modeling
ProteinML / Cited by Hunter – no other source?
SBML / The Systems Biology Markup Language (SBML) is a computer-readable format for representing models of biochemical reaction networks.
SimBios / technology infrastructure for physiome project
SysML / SysML is a domain-specific modeling language for systems engineering applications. Probably not relevant to this project; see SBML instead.
TissueML / Replaced by FieldML, per (June 2003)
UML / Unified Modeling Language, created by the Object Management Group.
UMLS / ‘The purpose of NLM's Unified Medical Language System (UMLS) is to facilitate the development of computer systems that behave as if they "understand" the meaning of the language of biomedicine and health.’
Visible Human Project / An NIH project started in 1998.
XML / Extensible Markup Language, a derivative of SGML (Standard Generalized Markup Language), defined by the World Wide Web Consortium (W3C).

See also for more MLs, and for other ontologies.

Vocabulary

Acinus – alveolus

AI – aortic insufficiency

Aneurysm – bulge in artery

ASD - atrial septal defect

CHF – congestive heart failure

Consilience – to demonstrate that ostensibly different ideas are really either compatible or the same. (Bass., 2000)

COPD - chronic obstructive pulmonary disease

Cytomics –study of the role of the cell within the context of genomics and proteomics discoveries. (from here)

Dipteran – of Diptera, 2-winged insect family

Fecundity – fertility

Genomics – study of the genome to understand its structure and function

Haptic – related to touch

Homothety - similarly placed.

Hyperdynamic – very fast pulse rate?

Hyperkinetic – abnormal or excessive movement

IBC – integrated (ultrasound) backscatter coefficient e.g. of coronary arteries

In silico – in a computer

In situ – in its natural place

In vitro – in an artificial environment (test tube)

In vivo – in a living organism

Ischemic – having inadequate blood supply

Kidri - ??

MI - myocardial infarction

MR – mitral (valve) regurgitation; similarly have AR, TR, and PR for the other valves

Omics – use of genome to help understand other previously existing fields of biology, e.g. other examples here.

Parenchyma – specialized tissue

PFO - patent foramen ovale (heart hole from placenta)

Pharmacogenomics – use of genome information to guide development or clinical use of drugs.

Phylogeny - the development over time of a species, genus, or group

Proteomics – use of genome information to understand protein formation

Semelparous – only reproduce once (salmon)

Senescence - growing old; aging.

Soma – body

Stenosis – abnormalconstriction or narrowing

Tautology – redundancy, or a logically true proposition

Major Aging Theories

Theory / Date / Description
Caloric restriction (CR)
(deMagalhaes, 2005) / 1935 / Eating less makes you live longer. May be connected to the GH/IGF-1 pathway.
Disposable Soma Theory(Kirkwood, 2000) / 1977 / To optimize resources between soma maintenance and reproduction, the latter wins to keep the species alive.
DNA damage
(deMagalhaes, 2005) / 1959 / Damage to DNA accumulates until it can’t be repaired, causing ageing. A.k.a. somatic mutation.
Free radical theories
(deMagalhaes, 2005) / 1956 / Free radicals and oxidants (reactive oxidative species, ROS) damage cell components – evidenced by UV, radiation, etc.
Mechanistic theories
(deMagalhaes, 2005) / 1963 / Three types: 1) DNA metabolism, 2) energy metabolism, and 3) growth factor (GH/IGF-1), plus a weirdo, klotho.
Network theory of aging (Kriete, 2006) / 1992 / Combines models of mt ROS production, aberrant proteins, free radicals, and scavengers (MARS)
Pleiotropy(Kirkwood, 2000) / Genes which help early in life later cause damage, but early benefit outweighs later cost.
Programmed Senescence
(Kirkwood, 2000) / 1961 / Senescence is programmed into animals in order to limit population. Very weak. Also called replicative senescence.
Rate of living theory
(deMagalhaes, 2005) / 1908 / Long-lived animals are bigger and exert less energy per unit mass than small ones. Aging is based on the rate of living. Very weak.
Shortening of telomeres
(Kriete, 2006) / Related to oxidative stress.

Dates mostly from (Kirkwood, 2003) and (deMagalhaes, 2005).

Papers

Journal articles moved to EndNote circa November 20, 2006. List here has been abbreviated…

Citation / Paper
(Bassingthwaighte, 2000) / Bassingthwaighte JB. Strategies for the physiome project. Annals of Biomedical Engineering. 28(8):1043-58, 2000 Aug.
(Bassingthwaighte, 2003) / Bassingthwaighte JB. The macro-ethics of genomics to health: the physiome project.Comptes Rendus Biologies. 326(10-11):1105-10, 2003 Oct-Nov.
(Bassingthwaighte, 2006) / James B. Bassingthwaighte, Howard Jay Chizeck, Les E. Atlas Strategies and Tactics in Multiscale Modeling of Cell-to-Organ Systems
Proceedings of the IEEE, VOL. 94, NO. 4, APRIL 2006
(Beard, 2001) / Beard DA. Computational framework for generating transport models from databases of microvascular anatomy.Annals of Biomedical Engineering. 29(10):837-43, 2001 Oct.
(Chatterjee, 2005) / Chatterjee A. Mayawala K. Edwards JS. Vlachos DG. Time accelerated Monte Carlo simulations of biological networks using the binomial tau-leap method.Bioinformatics. 21(9):2136-7, 2005 May 1.
(Crampin, 2004a) / Crampin EJ. Halstead M. Hunter P. Nielsen P. Noble D. Smith N. Tawhai M. Computational physiology and the Physiome Project. Experimental Physiology. 89(1):1-26, 2004 Jan.
(Crampin, 2004b) / Crampin EJ. Smith NP. Hunter PJ. Multi-scale modelling and the IUPS physiome project.Journal of Molecular Histology. 35(7):707-14, 2004 Sep.
(Dao, 2000) / Dao N. McCormick PJ. Dewey CF Jr. The human physiome as an information environment. Annals of Biomedical Engineering. 28(8):1032-42, 2000 Aug.
(deMagalhaes, 2005) / de Magalhaes, J.P., Open-minded scepticism: inferring the causal mechanisms of human ageing from genetic perturbations, Ageing Research Reviews, 4 (2005) 1-22.
(Du, 2005) / Du P. Gong J. Syrkin Wurtele E. Dickerson JA. Modeling gene expression networks using fuzzy logic.IEEE Transactions on Systems, Man, & Cybernetics, Part B: Cybernetics. 35(6):1351-9, 2005 Dec.
(El-Samad, 2006) / Hana El-Samad, Stephen Prajna, Antonis Papachristodoulou, John Doyle, Mustafa Khammash, Advanced Methods and Algorithms for Biological
Networks Analysis, Proceedings of the IEEE, VOL. 94, NO. 4, APRIL 2006
(Feig, 2004) / Feig M. Karanicolas J. Brooks CL 3rd. MMTSB Tool Set: enhanced sampling and multiscalemodeling methods for applications in structural biology.Journal of Molecular Graphics & Modelling. 22(5):377-95, 2004 May.
(Gavaghan, 2006) / Gavaghan D. Garny A. Maini PK. Kohl P. Mathematical models in physiology. Philosophical Transactions of the Royal Society London, Series a (Mathematical, Physical & Engineering Sciences). 364(1842):1099-106, 2006 May 15.
(Haulica, 2002) / Haulica I. From molecular genetics to functional genomics and physiome.Journal of Cellular & Molecular Medicine. 6(4):648-52, 2002 Oct-Dec.
(Hood, 2003) / Hood, Leroy, Systems biology: integrating technology, biology, and computation, Mechanisms of Ageing and Development 124 (2003) 9-16
(Hunter, 2002) / Peter Hunter · Peter Robbins · Denis Noble, The IUPS human physiome project, Eur J Physiol (2002) 445:1–9
(Hunter, 2002a) / Hunter PJ. Nielsen PM. Bullivant D. The IUPS Physiome Project. International Union of Physiological Sciences. Novartis Foundation Symposium. 247:207-17; discussion 217-21, 244-52, 2002.
(Hunter, 2004) / Hunter PJ. The IUPS Physiome Project: a framework for computational physiology. Progress in Biophysics & Molecular Biology. 85(2-3):551-69, 2004 Jun-Jul.
(Hunter, 2005a) / Hunter P. Smith N. Fernandez J. Tawhai M. Integration from proteins to organs: the IUPS Physiome Project. Mechanisms of Ageing & Development. 126(1):187-92, 2005 Jan.
(Hunter, 2005c) / Hunter P. Nielsen P. A strategy for integrative computational physiology. Physiology. 20:316-25, 2005 Oct.
(Hunter, 2006) / Peter J. Hunter, Modeling Human Physiology: The IUPS/EMBS Physiome Project, Proceedings of the IEEE, VOL. 94, NO. 4, APRIL 2006
(Kirkwood, 2000) / Kirkwood, T, Why do we age?, Nature, 408, 9 Nov 2000
(Kirkwood, 2003) / Kirkwood, T, Towards an e-biology of ageing: integrating theory and data, Nature Reviews, Molecular Cell Biology, v4, Mar 2003.
(Kirkwood, 2005) / Thomas B.L. Kirkwood, Understanding the Odd Science of Aging
Cell, Vol. 120, 437–447, February 25, 2005,
(Kitano, 2004) / Hiroaki Kitano, Biological Robustness, Nature Reviews Genetics 5, 826-837 (2004)
(Kohl, 2006) / Kohl P. Richard S. From funny current to current physiome.Progress in Biophysics & Molecular Biology. 90(1-3):1-4, 2006 Jan-Apr.
(Kriete, 2006) / Kriete, A, Systems approaches to the networks of aging, Ageing Research Reviews, xxx(2006) xxx-xxx.
(Mauroy, 2004) / B. Mauroy, M. Filoche, E. R. Weibel & B. Sapoval. 12 FEBRUARY 2004
An optimal bronchial tree may be dangerous. NATURE VOL 427
(Moore, 2004) / MooreMN. Noble D. Editorial: computational modelling of cell & tissue processes & function.Journal of Molecular Histology. 35(7):655-8, 2004 Sep.
(Raghothama, 2005) / Chaerkady Raghothama, H. C. Harsha1, C. K. Prasad & Akhilesh Pandey
Bioinformatics and proteomics approaches for aging research
Biogerontology (2005) 6: 227–232
(Rose, 2006) / Michael R. Rose, Casandra L. Rauser, Laurence D. Mueller, & Gregory Benford, A revolution for aging research
Biogerontology (2006) 7: 269–277
(Soti, 2006) / C. Soti, P. Csermely
Aging cellular networks: Chaperones as major participants
Experimental Gerontology xxx (2006) xxx–xxx
(Stroikin, 2005) / Yuri Stroikin, Helge Dalen, Ulf T. Brunk & Alexei Terman
Testing the ‘‘garbage’’ accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy
Biogerontology (2005) 6: 39–47
(Tawhai, 2000) / Tawhai, M.H., Pullan, A.J., Hunter, P.J., 2000. Generation of an anatomicallybased three-dimensional model of the conducting airways. Ann.Biomed. Eng. 28, 793–802.
(Tawhai, 2001a) / Tawhai, M.H., Hunter, P.J., 2001a. Characterising respiratory airway gas
mixing using a lumped parameter model of the pulmonary acinus.
Respir. Physiol. 127, 241–248.
(Tawhai, 2001b) / Tawhai, M.H., Hunter, P.J., 2001b. Multi-breath washout analysis: modeling the influence of conducting airway asymmetry. Respir. Physiol. 127, 249–258.
(Tracqui, 2006) / Philippe Tracqui, Mechanical Instabilities as a Central Issue for In Silico Analysis of Cell Dynamics, Proceedings of the IEEE, VOL. 94, NO. 4, APRIL 2006
(van Beek, 2006) / Johannes H. G. M. van Beek, Channeling the Data Flood: Handling Large-Scale Biomolecular Measurements In Silico
Proceedings of the IEEE, VOL. 94, NO. 4, APRIL 2006
(Viceconti, 2006) / Marco Viceconti, Debora Testi, Fulvia Taddei, Saulo Martelli, Gordon J. Clapworthy, Serge Van Sint Jan, Biomechanics Modeling of the Musculoskeletal Apparatus: Status and Key Issues, Proceedings of the IEEE, VOL. 94, NO. 4, APRIL 2006
Saudi Med J. 2006 Sep;27(9):1302-5. The role of heat shock proteins as chaperones on several human diseases.Mellati AA. Department of Biochemistry, ZanjanUniversity of Medical Sciences, Shahrak Karmandan, Zanjan, Iran.
Curr Pharm Des. 2006;12(24):3161-71. Inflamm-aging, cytokines and aging: state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology.Salvioli S, Capri M, Valensin S, Tieri P, Monti D, Ottaviani E, Franceschi C. Department of Experimental Pathology, University of Bologna, via S. Giacomo 12, Bologna, Italy.
J Endocrinol Invest. 2005;28(11 Suppl Proceedings):15-9. Links
The hormonal pathway to frailty in older men.Maggio M, Cappola AR, Ceda GP, Basaria S, Chia CW, Valenti G, Ferrucci L.
Clinical Research Branch, Longitudinal Studies Section, National Institute on Aging, National Institutes of Health, USA.
Apoptosis and Aging: Role of p66Shc Redox Protein. Enrica Migliaccio, Marco Giorgio, Pier Giuseppe Pelicci. Antioxidants & Redox Signaling. Mar 2006, Vol. 8, No. 3-4: 600-608
Nippon Naika Gakkai Zasshi. 2006 Mar 10;95(3):447-52.
[Anti-aging mechanism in centenarians][Article in Japanese]
Hirose N, Arai Y, Takayama M, Nakazawa S, Ebehara Y, Yamamura K, Gondo Y, Kojima T. PMID: 16640073 [PubMed - indexed for MEDLINE]
Int Wound J. 2005 Dec;2(4):364-8. Wound chronicity and fibroblast senescence--implications for treatment.Harding KG, Moore K, Phillips TJ. Wound Healing Research Unit, Department of Surgery, CardiffUniversity, Cardiff, UK.
Microcirculation. 2006 Jun;13(4):275-7.
The microcirculation of skeletal muscle in aging.Payne GW, Bearden SE.
Northern Medical Program, University of Northern British Columbia, Prince George, British Columbia, Canada.
Rejuvenation Res. 2006 Spring;9(1):143-8.
Biology of longevity: role of the innate immune system. Candore G, Colonna-Romano G, Balistreri CR, Di Carlo D, Grimaldi MP, Listi F, Nuzzo D, Vasto S, Lio D, Caruso C. Immunosenescence Unit, Department of Pathobiology and Biomedical Methodology, University of Palermo, Palermo, Italy.
Int J Sports Med. 2006 Feb;27(2):94-9.
Control of muscle size during disuse, disease, and aging. Degens H, Alway SE. Institute for Biophysical and Clinical Research into Human Movement, ManchesterMetropolitanUniversity, Alsager Campus, Alsager, Cheshire, UK.

Books

Multiscale and Multiresolution Methods

Theory and Applications, Series: Lecture Notes in Computational Science and Engineering , Vol.20, Barth, Timothy J.; Chan, Tony; Haimes, Robert (Eds.)
2002, X, 392 p., 118 illus., 11 in colour, Softcover, ISBN: 3-540-42420-2

Mathematical Physiology

Series: Interdisciplinary Applied Mathematics , Vol.8, Keener, James, Sneyd, James
1st ed. 1998. Corr. 2nd printing, 2001, XIX, 766 p., 347 illus., Hardcover, ISBN: 0-387-98381-3

Title Robustness and evolvability in living systems / Andreas Wagner.

Imprint Princeton, N.J. : Princeton University Press, c2005.

ISBN 0691122407 (cloth : alk. paper)

Title Microbial phylogeny and evolution [electronic resource] : concepts and controversies / edited by Jan Sapp., Imprint New York : Oxford University Press, 2005.

ISBN 0195168771 (alk. paper)

Computational Systems Biology

by Andres Kriete (Editor), Roland Eils (Editor)

ISBN: 012088786X, Publisher: Elsevier Science & Technology Books