Biology Reference
In-Depth Information
Chapter 3
Interactome Networks
Anne-Ruxandra Carvunis
1
,
2
, Frederick P. Roth
1
,
3
, Michael A. Calderwood
1
,
2
, Michael E. Cusick
1
,
2
,
Giulio Superti-Furga
4
and Marc Vidal
1
,
2
1
Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA,
2
Department
of Genetics, Harvard Medical School, Boston, MA 02115, USA,
3
Donnelly Centre for Cellular & Biomolecular Research, University of Toronto, Toronto,
Ontario M5S-3E1, Canada, & Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario M5G-1X5, Canada,
4
Research Center for
Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
Chapter Outline
Introduction
45
Predicting Gene Functions, Phenotypes and Disease
Associations
Life Requires Systems
45
53
Cells as Interactome Networks
46
Assigning Functions to Individual Interactions, Protein
Complexes and Network Motifs
Interactome Networks and Genotype
Phenotype
54
e
Relationships
47
Towards Dynamic Interactomes
55
Mapping and Modeling Interactome Networks
47
Towards Cell-Type and Condition-Specific
Interactomes
Towards a Reference Protein
e
Protein Interactome Map
48
55
Strategies for Large-Scale Protein
e
Protein Interactome
Evolutionary Dynamics of Protein
e
Protein Interactome
Mapping
48
Networks
56
Large-Scale Binary Interactome Mapping
49
Concluding Remarks
57
Large-Scale Co-Complex Interactome Mapping
50
Acknowledgements
58
Drawing Inferences from Interactome Networks
51
References
58
Refining and Extending Interactome Network Models
51
INTRODUCTION
Life Requires Systems
What is Life? The answer to the question posed by
Schr
ยจ
dinger in a short but incisive topic published in 1944
remains elusive more than seven decades later. Perhaps
a less ambitious, but more pragmatic question could be:
what does Life require? Biologists agree on at least four
fundamental requirements, among which three are palpable
and easily demonstrable, and a fourth is more intangible
(
Figure 3.1
). First, Life requires chemistry. Biomolecules,
including metabolites, proteins and nucleic acids, mediate
the most elementary functions of biology. Life also requires
genes to encode and 'reproduce' biomolecules. For most
organisms, cells provide the fundamental medium in which
biological processes take place. The fourth requirement is
evolution by natural selection. Classically, these 'four great
ideas of biology'
[1]
have constituted the main intellectual
framework around which biologists formulate biological
questions, design experiments, interpret data, train younger
generations of scientists and attempt to design new thera-
peutic strategies.
The next question then should be: even if we fully
understood each of these four basic requirements of
biology, would we be anywhere near a complete under-
standing of how Life works? Would we be able to fully
explain genotype
phenotype relationships? Would we be
able to fully predict biological behaviors? How close would
we be to curing or alleviating suffering from human
diseases? It is becoming clear that even if we knew
everything there is to know about the four currently
accepted requirements of biology, the answer to 'What Life
is' would remain elusive.
The main reason is that biomolecules do not function in
isolation, nor do cells, organs or organisms, or even
ecosystems and sociological groups. Rather, biological
entities are involved in intricate and dynamic interactions,
thereby forming 'complex systems'. In the last decade,
novel biological questions and answers have surfaced, or
resurfaced, pointing to systems as a fifth fundamental
e
