Pathway diagrams are used by life scientists to represent complex interactions at the molecular level in living cells. The recent shift towards data-intensive bioinformatics and systems-level science has created a strong need for advanced pathway visualizations that support exploratory analysis. This paper presents a comprehensive list of requirements for pathway visualization systems, based on interviews conducted to understand life scientists' needs for pathway analysis. A variety of existing pathway visualization systems are examined, to analyze common approaches by which the contemporary systems address these requirements. A heuristic evaluation, by biology domain experts, of five popular pathway visualization systems is conducted to analyze the end-user perception of these systems. Based on these studies, a research agenda is presented concerning five critical requirements for pathway visualization systems. If addressed effectively, these requirements can prove to be most helpful in supporting exploratory pathway analysis. These include: (1) automated construction and updating of pathways by searching literature databases, (2) overlaying information on pathways in a biologically relevant format, (3) linking pathways to multi-dimensional data from high-throughput experiments such as microarrays, (4) overviewing multiple pathways simultaneously with interconnections between them, (5) scaling pathways to higher levels of abstraction to analyze effects of complex molecular interactions at higher levels of biological organization.
ChurchillG. Fundamentals of experimental design for cDNA microarrays. Nature Genetics2002; 32: 490–495.
4.
QuackenbushJ. Microarray data normalization and transformation. Nature Genetics2002; 32: 496–501.
5.
BIOCARTA. Charting pathways of life [WWW document]. www.biocarta.com (accessed 24 April 2005).
6.
ScheidelerMSchlaichNFellenbergKBeissbarthTHauserNVingronMSlusarenkoAHoheiselJ. Monitoring the switch from housekeeping to pathogen defense metabolism in Arabidopsis thaliana using cDNA arrays. Journal of Biological Chemistry2002; 277: 10555–10561.
7.
LodishHBerkAZipurskySMatsudairaPBaltimoreDDarnellJ. Molecular Cell Biology.W.H. Freeman, New York, 2000.
8.
Kanehisha Laboratories. KEGG: Kyoto Encyclopedia of Genes and Genomes. [WWW document] http://www.genome.jp/kegg/ (accessed 24 April 2005).
9.
DahlquistKSalomonisNVranizanKLawlorSConklinB. GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nature Genetics2002; 31: 19–20.
StevensRGobleCBakerPBrassA. A classification of tasks in bioinformatics. Bioinformatics2001; 17: 180–188.
12.
MichalG. On representation of metabolic pathways. BioSystems1998; 47: 1–7.
13.
PurchaseHC. Metrics for graph drawing aesthetics. Journal of Visual Languages and Computing2002; 13: 501–516.
14.
WareCPurchaseHColpoysLMcGillM. Cognitive measurements of graph aesthetics. Information Visualization2002; 1: 103–110.
15.
ShannonPMarkielAOzierOBaligaNWangJRamageDAminNSchwikowskiBIdekerT. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Research2003; 13: 2498–2504.
16.
RossonMCarrollJ. Usability Engineering: Scenario-Based Development of Human Computer Interaction.Morgan Kauffman, Los Altos, CA, 2001.
17.
NielsenJ. Finding usability problems through heuristic evaluation. In Proceedings of CHI 92.ACM Press, New York373–380.
18.
The alliance for cellular signaling (AfCS). Nature2002; 420: 6916.
19.
HeathLRamakrishnanN. The emerging landscape of bioinformatics software system. IEEE Computing2002; 35: 41–45.
20.
SaraiyaPNorthCDucaK. An insight-based methodology for evaluating bioinformatics visualization. IEEE Transactions on Visualization and Computer Graphics2005; 11: 443–456.
KarpPCollado-VidesJIngrahamJPaulsenISaierM. Ecocyc: Encyclopedia of Escherichia coli K12 Genes and Metabolism. [WWW document], http://www.ecocyc.org/ (accessed 24 April 2005).
28.
KrishnamurthyLNadeauJOzsoyogluZMOzsoyogluGSchaefferGTasanMXuW. Pathways database system: An integrated system for biological pathways. Bioinformatics2003; 19: 930–937.
29.
ToyodaTHirosawaKKonagayaA. KnowledgeEditor: A new tool for interactive modeling and analyzing biological pathways based on microarray data. Bioinformatics2003; 19: 433–434.
30.
LeeMHyunSParkS. UniPath: A knowledge representation system for biological pathways. Genome Informatics2003; 14: 681–682.
31.
YaoDQuKWangJLuYNobleNSunHZhuXLinNPayanDLiM. PathwayFinder: paving the way towards automatic pathway extraction. Proceedings of the Second Conference on Asia-Pacific Bioinformatics. (Dunedin, New Zealand) 2004; 2: 53–62.
FriedmanCKraPYuHKrauthammerMRzhetskyA. GENIES: A natural-language processing system for the extraction of molecular pathways from journal articles. Bioinformatics2001; 17: S74–82.
ZupanBDemsarJBratkoIJuvanPHalterJKuspaAShaulskyG. GenePath: A system for automated construction of genetic networks from mutant data. Bioinformatics2003; 19: 383–389.
37.
GlassÄGierlI. Proceedings of Second International Conference of Biosystems and Medical Technology, September 7–9, 2000 (Rostock-Warnemunde, Germany) 2000; 52 pp.
DemirEBaburODogrusozUGursoyANisanciGCetin-AtalayROzturkM. PATIKA: An integrated visual environment for collaborative construction and analysis of cellular pathways. Bioinformatics2002; 18: 996–1003.
40.
KuchinskyAGrahamKMohDCreechM. Biological storytelling: a software tool for biological information organization based upon narrative structure. Proc ACM Advanced Visual Interfaces Conference (Trento, Italy) 2002.
41.
ToyodaTMochizukiYKonagayaA. GSCOPE: A clipped fisheye viewer effective for highly complicated biomolecular network graphs. Bioinformatics2003; 19: 437–438.
42.
GeneSpring™. Silicon Genetics. www.silicongenetics.com [WWW document], (accessed 24 April 2005).
43.
ThimmOBiäsingOGibonYNagelAMeyerSKrügerPSelbigJMüllerLRheeSStittM. MAPMAN: A user-driven tool to display genomics data sets onto diagrams of metabolic pathways and other biological processes. The Plant Journal2004; 37: 914–939.
44.
DonigerSSalomonisNDahlquistKVarnizanKLawlorSConklinB. MAPPFinder: Using Gene Ontology and GenMAPP to create a global gene expression profile from microarray data. Genome Biology2003; 4: R7.
TufteE. The Visual Display of Quantitative Information (Graphic Press, Cheshire, CT) 1983.
47.
MarkielA. Cytoscape: a network modeling environment with applications to biomolecular interaction networks. The IEEE Symposium on Information Visualization. (Seattle, Washington) 2003; Interactive Demos.
48.
HermanIMelanconGMarshallM. Graph visualization and navigation in information visualization: A survey. IEEE Transactions on Visualization and Computer Graphics2000; 6: 24–43.
49.
BedersonBHollanJ. Pad++: a zooming graphical interface for exploring alternate interface physics. In Proceedings of User Interface Software and Technology (UIST 94)1994. ACM Press, New York, 17–26.
50.
FeinerS. Seeing the forest for the trees: Hierarchical display of hypertext structure. Proceedings of the ACM Conference on Office Information Systems (Palo Alto, CA, March) 1988; 205–222.
