Comprehensive data-driven analysis of the impact of chemoinformatic structure on the genome-wide biological response profiles of cancer cells to 1159 drugs

Table 1 Summarized interpretation of top 10 components. Group A and B are the subcomponents of Figure 3

Comp.	Biological Interpretation	Compounds in Group A	Compounds in Group B	VolSurf Interpretation
1	Classic growth factor signaling: (MAP and protein kinase signaling)	Sulfonamides, antibiotics, carbonic anhydrase inhibitors	Antipsychotic and antihistaminic compounds	High lipophilicity
2	DNA damage	Contrast agents, antibiotics,	DNA damaging agents, antimetabolites	Strong lipophilic areas emphasized
3	Stress response, mitochondrial and anabolic metabolism	DNA damaging agents	GPCR antagonists, ion channel blockers	Polar interactions enriched
4	Cytoskeleton, cell adhesion and migration	GPCR liganda, macrocyclic cmpds and contrast agents	Beta adrenergic agonists, other GPCR ligands	N/A
5	Differentiation, EMT, stemness	NSAIDS, cAMP signaling promoting compounds	HDAC Inhibitors, HDAC-like	Significantly enriched with pharmacophoric features*
6	Inflammatory and differentiation signaling	N/A	Protein synthesis inhibitors, anti-diabetics, cardiac glycosides	Pharmacophoric features*
7	GPCR and cytokine signaling	N/A	Cardiac glycosides, cephalosporins	Pharmacophoric features*
8	Growth factor and cell adhesion signaling	Cardiac glycosides	β-adrenergic agonists, Ca²⁺ channel blockers	Integy-moment and significant pharmacophoric enriched*
9	Amino acid and nitrogen metabolism	Protein synthesis inhibitors	Anti-diabetics	Integy-moment and significant pharmacophoric enriched*
10	Cancer signaling	DNA damaging agents	Corticosteroids, ionophores	Size shape type descriptors

The pharmacophoric enrichment analysis (marked with “*”) was carried out over VolSurf features (Additional file 5: VolSurf_Classification.xls) considered as a gold standard, and measuring enrichment of the list in a component by a hypergeometric test.

ISSN: 1471-2105