A method and server for predicting damaging missense mutations

IA Adzhubei, S Schmidt, L Peshkin, VE Ramensky… - Nature …, 2010 - nature.com
Nature methods, 2010nature.com
2). For instance, in this setting with m= 10 and q= 10, IDA found 4, 4, 5, 1 and 2 true positives
for the five different networks, whereas Lasso found 1, 1, 0, 1 and 2 true positives and Elastic-
net found 3, 1, 0, 1 and 1 true positives. The results presented here on S. cerevisiae and the
DREAM4 data are proof-of-concept results that IDA can predict the strongest causal effects
in potentially large-scale biological systems by using only observational data. In particular,
the results on S. cerevisiae demonstrate that we were able to do this in a challenging real …
2). For instance, in this setting with m= 10 and q= 10, IDA found 4, 4, 5, 1 and 2 true positives for the five different networks, whereas Lasso found 1, 1, 0, 1 and 2 true positives and Elastic-net found 3, 1, 0, 1 and 1 true positives. The results presented here on S. cerevisiae and the DREAM4 data are proof-of-concept results that IDA can predict the strongest causal effects in potentially large-scale biological systems by using only observational data. In particular, the results on S. cerevisiae demonstrate that we were able to do this in a challenging real-world setting where the number of variables (5,361) was much larger than the sample size (63) and the variables were substantially disturbed by noise. As IDA is supported by mathematical theory, we expect the results presented here to generalize to other problems.
Of course, statistical predictions based on observational data can never replace intervention experiments. In fact, whenever possible, IDA predictions should be followed up by intervention experiments. In this way, the predictions can serve as a new tool for the design of experiments, as they indicate which interventions are likely to show a large effect. Software for IDA is available in the open source R-package pcalg (http://cran. r-project. org/web/packages/pcalg/index. html).
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