We propose the "most diverse reference panel", defined as the subset with the maximal "phylogenetic diversity", thereby incorporating individuals that span a diverse range of genotypes within the sample.
We propose the use of the most diverse reference panel for genotype imputation, adapting the greedy algorithm for maximizing phylogenetic diversity in our selection of an internal reference panel.
Clearly, a large and structurally diverse reference set is essential to the similarity based approaches.
Diverse reference shape selection for the one million compound dataset was performed in two stages.
In our study we introduce relatively simple and effective test beds to collect accurate and diverse reference data.
However, the shape space of the remaining 0.2% conformers increases the number of diverse reference shapes from 2 458 to 5 534.
This observation suggests that a sufficiently large and diverse reference library is important for the predicting accuracy, which explains why the target fishing problem should be addressed from a "big data" perspective.
The diverse reference shapes used in this work (see Additional files1 and 2) should be useful in helping create the initial reference shapes required to implement this method for arbitrary conformer databases.
Our results indicate the following sequencing study design guidelines which take advantage of the recent advances in genotype imputation methodology: Select the largest and most diverse reference panel for sequencing and genotype as many "anchor" markers as possible.
For three gene families, we created 240 additional simulated datasets using the diverse reference databases.
For all sequence lengths considered, the most diverse reference panels provide lower discordance rates than the randomly selected reference panels.
