Nucleic Acids Research, 2008, Vol. 36, Database issue D73 Table 1. Summary of chain 153 containing gene glp-1 Bicluster Type Set 1 Set 2 1 2 3 Gene-phenotype nmy-1, par-1 Gene-GO apx-1, glp-1, nmy-1, par-1 Gene-gene glp-1, par-1 PBPhen25 (Asymmetry of division), WBPhen30 (Embryonic lethal), WBPhen301 (Protruding vulva), WBPhen320 (Sterile), WBPhen326 (Sterile progeny), WBPhen7 (Asymmetry of division abnormal) GO:0002119 [Larval dev. (sensu Nematoda)], GO:0044464 (Cell part), GO:0009987 (Cellular process), GO:0048856 (Anatomical structure dev.), GO:0007389 (Pattern speciﬁcation process), GO:0009790 (Embryonic dev.), GO:0009791 (Post-embryonic dev.) glp-1, par-1 suggest that genes in this chain contribute to the structural aspects of cell division such as pattern speciﬁcation leading to asymmetry of division, and these might be important to avoid embryonic lethality, protruding vulva and sterile progeny. Furthermore, this set of genes is likely to be self-regulated. Four genes characterize the two chains: par-1, apx-1, nmy-2 and glp-1. Par-1 encodes a serine threonine kinase, which is required for the spatial regulation of GLP-1 asymmetry (39). Par-1 is connected to glp-1 through the GO and gene regulation blocks. Apx-1 encodes a ligand homolog to the Delta protein of Drosophila. Both proteins contribute to the establishment of the dorsal- ventral axis in the early C. elegans embryo (40). Chains 153 and 154 suggest an interaction between par-1 and apx-1. The likelihood of this prediction is further strength- ened by the computational prediction of interaction between the same pair of genes (or their products) by Zhong and Sternberg (41). A putative gene in the Notch pathway is nmy-2, which encodes a maternally expressed non-muscle myosin II. The corresponding protein is linked through the phenotype bicluster containing par-1. The function of NMY-2 and PAR-5 is to together establish polarization in the C. elegans zygote along the anterior–posterior axis 23. In summary, glp-1 and par-1 interaction was already suggested, while apx-1 and nmy-2 represent new potential interactions with glp-1 in the LIN-12/Notch pathway, uncovered through CDM. Wnt pathway The Wnt signal transduction pathway regulates diverse processes including cell proliferation, migration, polarity, diﬀerentiation and axon outgrowth in C. elegans. The signaling is composed of two pathways, the canonical wnt/BAR-1 pathway and the non-canonical wnt/WRM-1 pathway. A common component in both pathways is the HMG box containing protein POP-1, which is a member of the TCF/LEF family of TFs. The wnt-signaling pathway regulates the activation of the latter (42,43). CMGSDB reported 32 chains containing pop-1, the common target of the two wnt-pathways. These 32 chains suggested 18 new gene candidates (daf-2, par-2, par-3, par-5, par-6, pkc-3, pkc-6, ooc-3, gpa-16, mbk-2, mes-1, csn-3, pgl-1, egl-46, tac-1, rab-5, tba-2, uri-1) for the pathway. Of these, only par-5 (chains 234, 236, 240) has been conﬁrmed as a regulator of pop-1 (44). pop-1 is connected to par-2 (chains 204, 206, 210, 212) through a regulatory network (45,46). Consistent with the results from CMGSDB, Zhong and Sternberg (41) predicted interactions between par-2, mes-1 (chains 246, 248), a gene encoding a tyrosine kinase-like protein that is required for unequal cell division (47), ooc-3 (chains 222, 224), encoding a protein required to establish asymme- trical anterior–posterior cortical domains and spindle orientation (48), and gpa-16 (chains 234, 236), encoding a member of the G-protein alpha-subunit family of hetero- chromatic GTPase that eﬀects spindle position and orientation (49). It can be hypothesized that PAR-2 is regulated by POP-1 over PAR-5. Further evidence shows that PAR-2 is regulated independently from the wnt- pathway, as it is not regulated by MOM-5 and MOM-2, the wnt-receptor and wnt-ligand, respectively (50). From the above gene list of 18 genes, CMGSDB suggests an interaction of wnt-proteins with the tyrosine kinase receptor DAF-2, which is involved in longevity and insulin signaling. This can be a potential link between daf- proteins and wnt-pathway proteins, indicating a possible connection between insulin and wnt signaling. Some database statistics In this section, we describe some basic statistics about the data in CMGSDB, especially focusing on data related to RNAi experiments and phenotypes and chains. Figure 4 illustrates some of the statistics of chains. Chains consisting of 3, 4 and 5 biclusters, number 2054, 1654 and 426, respectively. Figure 4 examines the distri- bution of the total number of genes in a chain and the number of common genes among all biclusters in a chain. CMGSDB stores 81 722 RNAi experiments and 565 RNAi phenotypes. This includes 145 028 relationships between 21 222 unique C. elegans gene transcripts and the above 565 phenotypes. PHENOTYPE BROWSER In CMGSDB, phenotypes from several diﬀerent sources have been organized into a common hierarchy. This hierarchy is available for browsing via a phenotype browser available at https://bioinformatics.cs.vt.edu/ cmgs/CMGSDB/Treeview/index.php. The viewer has