Filtern
Erscheinungsjahr
- 2014 (2) (entfernen)
Dokumenttyp
- Wissenschaftlicher Artikel (2) (entfernen)
Sprache
- Englisch (2)
Volltext vorhanden
- ja (2)
Gehört zur Bibliographie
- nein (2) (entfernen)
Institut
- Medizin (2) (entfernen)
Computational analyses of functions of gene sets obtained in microarray analyses or by topical database searches are increasingly important in biology. To understand their functions, the sets are usually mapped to Gene Ontology knowledge bases by means of over-representation analysis (ORA). Its result represents the specific knowledge of the functionality of the gene set. However, the specific ontology typically consists of many terms and relationships, hindering the understanding of the ‘main story’. We developed a methodology to identify a comprehensibly small number of GO terms as “headlines” of the specific ontology allowing to understand all central aspects of the roles of the involved genes. The Functional Abstraction method finds a set of headlines that is specific enough to cover all details of a specific ontology and is abstract enough for human comprehension. This method exceeds the classical approaches at ORA abstraction and by focusing on information rather than decorrelation of GO terms, it directly targets human comprehension. Functional abstraction provides, with a maximum of certainty, information value, coverage and conciseness, a representation of the biological functions in a gene set plays a role. This is the necessary means to interpret complex Gene Ontology results thus strengthening the role of functional genomics in biomarker and drug discovery.
Consequences of a human TRPA1 genetic variant on the perception of nociceptive and olfactory stimuli
(2014)
Background: TRPA1 ion channels are involved in nociception and are also excited by pungent odorous substances. Based on reported associations of TRPA1 genetics with increased sensitivity to thermal pain stimuli, we therefore hypothesized that this association also exists for increased olfactory sensitivity.
Methods: Olfactory function and nociception was compared between carriers (n = 38) and non-carriers (n = 43) of TRPA1 variant rs11988795 G.A, a variant known to enhance cold pain perception. Olfactory function was quantified by assessing the odor threshold, odor discrimination and odor identification, and by applying 200-ms pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and heat stimuli, and 200-ms intranasal pulses of CO2).
Results: Among the 11 subjects with moderate hyposmia, carriers of the minor A allele (n = 2) were underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049). Moreover, carriers of the A allele discriminated odors significantly better than non-carriers (13.161.5 versus 12.361.6 correct discriminations) and indicated a higher intensity of the H2S stimuli (29.2613.2 versus 21612.8 mm VAS, p = 0.006), which, however, could not be excluded to have involved a trigeminal component during stimulation. Finally, the increased sensitivity to thermal pain could be reproduced.
Conclusions: The findings are in line with a previous association of a human TRPA1 variant with nociceptive parameters and extend the association to the perception of odorants. However, this addresses mainly those stimulants that involve a trigeminal component whereas a pure olfactory effect may remain disputable. Nevertheless, findings suggest that future TRPA1 modulating drugs may modify the perception of odorants.