Gene Function Prediction

About 31% of human gene names do not appear in MEDLINE, nor do approximately 90% of human non-coding RNAs. And existing literature is heavily skewed towards well-known genes with 75% of effort focusing on 10% of genes (Edwards et al., 2011). We can predict what individual genes do and find genes related to phenotypes/diseases of interest (e.g., synaptic transmission, sarcopenia). We have developed software that analyzes over 75,000 human microarray experiments to identify genes correlated across heterogeneous conditions (Dozmorov & Wren, 2011a,b; Wren, 2009) that can then be linked back to what they have in common in MEDLINE (Figure). Phenotype prediction has been 85% accurate in wet-lab experiments (48 positive out of 56 tested) and several formerly uncharacterized genes successfully validated (Towner et al, 2013a; Towner et al., 2013b; Clemmensen et al., 2012; Lupu et al., 2011; Daum et al., 2009).
 

References:

Clemmensen, S.N., Bohr, C.T., Rorvig, S., Glenthoj, A., Mora-Jensen, H., Cramer, E.P., Jacobsen, L.C., Larsen, M.T., Cowland, J.B., Tanassi, J.T. et al. (2012). Olfactomedin 4 defines a subset of human neutrophils. J. Leukocyte Biol. 91, 495-500.

Daum, J.R., Wren, J.D., Daniel, J.J., Sivakumar, S., McAvoy, J.N., Potapova, T.A., and Gorbsky, G.J. (2009). Ska3 is required for spindle checkpoint silencing and the maintenance of chromosome cohesion in mitosis. Current Biol. 19,1467-1472.

Dozmorov, M.G., and Wren, J.D. (2011a) High-throughput processing and normalization of one-color microarrays for transcriptional meta-analyses. BMC Bioinformatics  12 Suppl 10:S2.

Dozmorov, M.G., Giles, C.B., and Wren, J.D. (2011b). Predicting gene ontology from a global meta-analysis of 1-color microarray experiments. BMC Bioinformatics 12 Suppl 10:S14.

Edwards, A.M., Isserlin, R., Bader, G.D., Frye, S.V., Willson, T.M., and Yu, F.H. (2011). Too many roads not taken. Nature 470,163-165.

Lupu, C., Zhu, H., Popescu, N.I., Wren, J.D., and Lupu, F. (2011). Novel protein ADTRP regulates TFPI expression and function in human endothelial cells in normal conditions and in response to androgen. Blood 118, 4463-4471.

Towner, R.A., Jensen, R.L., Vaillant, B., Colman, H., Saunders, D., Giles, C.B., and Wren, J.D. (2013a) Experimental validation of 5 in-silico predicted glioma biomarkers. Neuro-oncology 15,1625-1634.

Towner, R.A., Jensen, R.L., Colman, H., Vaillant, B., Smith, N., Casteel, R., Saunders, D., Gillespie, D.L., Silasi-Mansat, R., Lupu, F. et al. (2013b). ELTD1, a potential new biomarker for gliomas. Neurosurgery  72,77-90.

Wren, J.D. (2009). A global meta-analysis of microarray expression data to predict unknown gene functions and estimate the literature-data divide. Bioinformatics  25,1694-1701.