Phenotypic noise

Investigating phenotypic diversity is not easy. A basic requirement is to have different lines of parasite available and in natural host species. However, being aware of the possibility of variation between individual worms would be a start. The few studies that have molecularly considered individual worms (Bianco et al., 1990 Fraser and Kennedy, 1990 Currie et al., 1998) have found variation between individual worms. Such variation may be the basis of some experimental noise . Perhaps efforts should be focused on this noise The phenotypic diversity that exists in natural, and even laboratory, populations of nematodes is maintained there by natural selection. This tells us, anthropomorphically, that such diversity matters to parasitic nematodes. It is hoped that this chapter has shown that it should also matter to us. 

After the selection of the specific techniques to be employed, one must determine how to quantify the genes associated with the phenotype of interest. The design of an assay that acts as a reporter or a molecular sensor can prove to be the most challenging step in designing a successful RNAi screen. The assay must be both highly reproducible and sensitive, without noise, and exhibiting minimal standard error. Traditional assay development techniques must be taken into account for all RNAi screens as they are for conventional compound-based screens. 

The environmental deviation acts on the genotypic values - a and + a as a Gaussian noise, so that the phenotypic values of the individuals of the... 

For assessment of dominant lethals, it is essential to avoid noise as much as possible. The largest fraction of the experimental noise comes from embryos that die from recessive lethals accumulated in the genome of the strains used. Since many recessive lethal mutations occur spontaneously and are accumulated in the genome, these cannot be distinguished phenotypically from dominant lethals. Hence, the use of inbred or narrowly maintained strains should be avoided. Instead, the test of dominant lethals using a hybrid will prove to be much more useful. 

Fig. 4 Calculation of SNR and heatmap representation. The signal-to-noise ratio (SNR) represents the degree to which a compound induces a phenotype that is distinct in mutant versus wild-type cell lines. Compounds with the most positive and most negative SNR represent the compounds that best discriminate between the two classes of cells, and may be depicted in a heatmap (analogous to gene expression data)...

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