Depicting combinatorial complexity with the molecular interaction map notation.
To help us understand how bioregulatory networks operate, we need a standard notation for diagrams analogous to electronic circuit diagrams. Such diagrams must surmount the difficulties posed by complex patterns of protein modifications and multiprotein complexes. To meet that challenge, we have designed the molecular interaction map (MIM) notation (http://discover.nci.nih.gov/mim/). Here we show the advantages of the MIM notation for three important types of diagrams: (1) explicit diagrams that define specific pathway models for computer simulation; (2) heuristic maps that organize the available information about molecular interactions and encompass the possible processes or pathways; and (3) diagrams of combinatorially complex models. We focus on signaling from the epidermal growth factor receptor family (EGFR, ErbB), a network that reflects the major challenges of representing in a compact manner the combinatorial complexity of multimolecular complexes. By comparing MIMs with other diagrams of this network that have recently been published, we show the utility of the MIM notation. These comparisons may help cell and systems biologists adopt a graphical language that is unambiguous and generally understood.
Kohn
Kurt W
KW
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA. kohnk@dc37a.nci.nih.gov
Aladjem
Mirit I
MI
Kim
Sohyoung
S
Weinstein
John N
JN
Pommier
Yves
Y
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003198:Computer Simulation; D003626:Data Display; D066246:ErbB Receptors / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry; D018739:Oncogene Proteins v-erbB / Q000737:chemistry; D011485:Protein Binding; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D012984:Software; D009626:Terminology as Topic
D046912:Multiprotein Complexes; D018739:Oncogene Proteins v-erbB; D066246:ErbB Receptors