Table 1.
Functional profile of the imatinib-induced transcriptional response
| KS | CM | AD | ZA | ZK | ZC | D1 | D2 | D3 | D4 | D5 | D6 | ΔZC | ΔZK | Size* | Biological process (GO) |
| + | + | -1.00 | -1 | 3 | 'de novo' IMP biosynthesis | ||||||||||
| + | + | + | + | + | + | + | + | + | + | + | +1.00 | +1 | 5 | Heme biosynthesis | |
| + | -1.00 | -1 | 3 | Inactivation of MAPK activity | |||||||||||
| + | + | -1.00 | -1 | 5 | Intracellular transport | ||||||||||
| + | -1.00 | -1 | 5 | Negative regulation of apoptosis | |||||||||||
| + | -0.87 | -1 | 22 | Regulation of transcription | |||||||||||
| + | + | -0.97 | -1 | 7 | Regulation of translational initiation | ||||||||||
| + | + | -1.00 | -1 | 7 | Translational initiation | ||||||||||
| KS | CM | AD | ZA | ZK | ZC | D1 | D2 | D3 | D4 | D5 | D6 | ΔZC | ΔZK | Size* | Biological process (ABI) |
| + | + | + | +1.00 | +1 | 17 | Hematopoiesis | |||||||||
| + | + | + | + | -1.00 | -1 | 25 | Inhibition of apoptosis | ||||||||
| + | + | + | + | + | -0.89 | -1 | 9 | Macrophage-mediated immunity | |||||||
| + | + | + | + | + | -0.99 | -1 | 37 | MAPKKK cascade | |||||||
| + | + | + | + | -1.00 | -1 | 21 | Protein complex assembly | ||||||||
| + | -1.00 | -1 | 4 | rRNA metabolism | |||||||||||
| KS | CM | AD | ZA | ZK | ZC | D1 | D2 | D3 | D4 | D5 | D6 | ΔZC | ΔZK | Size* | Molecular function (GO) |
| + | + | + | + | -0.90 | -1 | 257 | ATP binding | ||||||||
| + | -0.61 | -1 | 17 | ATP-dependent helicase activity | |||||||||||
| + | + | + | + | + | -0.91 | -1 | 57 | GTPase activity | |||||||
| + | + | + | + | + | -1.00 | -1 | 3 | Protein kinase C activity | |||||||
| + | -1.00 | -1 | 6 | Protein tyrosine phosphatase activity | |||||||||||
| + | + | + | + | + | + | -0.93 | -1 | 95 | RNA binding | ||||||
| + | + | + | + | + | -0.91 | -1 | 14 | Translation initiation factor activity | |||||||
| KS | CM | AD | ZA | ZK | ZC | D1 | D2 | D3 | D4 | D5 | D6 | ΔZC | ΔZK | Size* | Molecular function (ABI) |
| + | -0.87 | -1 | 18 | Protein kinase | |||||||||||
| KS | CM | AD | ZA | ZK | ZC | D1 | D2 | D3 | D4 | D5 | D6 | ΔZC | ΔZK | Size* | Molecular pathway (ABI) |
| + | -1.00 | -1 | 23 | EGR receptor signaling pathway | |||||||||||
| + | + | + | + | + | + | + | + | -1.00 | -1 | 8 | Interferon-gamma signaling pathway | ||||
| + | + | + | + | -1.00 | -1 | 3 | Metabotropic glutamate receptor group I pathway | ||||||||
| KS | CM | AD | ZA | ZK | ZC | D1 | D2 | D3 | D4 | D5 | D6 | ΔZC | ΔZK | Size* | Cellular component (GO) |
| + | + | + | + | -1.00 | -1 | 147 | Cytoplasm | ||||||||
| + | + | + | + | +1.00 | +1 | 4 | Kinesin complex | ||||||||
| + | + | + | + | + | + | + | +0.73 | +1 | 9 | Microtubule associated complex | |||||
| + | + | + | + | -0.93 | -1 | 23 | Nuclear pore | ||||||||
| + | + | + | -1.00 | -1 | 24 | Nucleolus | |||||||||
| + | + | -1.93 | -1 | 21 | Ribonucleoprotein complex | ||||||||||
Gene categories in the imatinib data (P.H., B.N., A Andersson, C Lassen, U Gullberg, and T.F., unpublished work) called significant by at least one of the category-detection methods (25% false-discovery rate; significance indicated by +). Key observations: (1) The choice of method strongly influences the results. (2) The method-method agreements observed on real data approximately follow those observed in the simulations (see Figure 3). (3) Several detected categories are consistent with literature data on BCR/ABL1-mediated leukemogenesis, supporting the validity of the methodology (see main text). (4) The table illustrates the use of indicator functions to determine the direction of transcriptional deviation in detected categories. In this case, ZC and ZK exemplify soft indicators (available for AD, CM, ZA, and ZC) and the less informative hard indicators (available for KS and ZK), respectively (see also Figure 5). *By size, we mean the number of unique genes (Entrez Gene IDs) within the category.