I am incredibly excited to share that I received an offical notice of award for my NSF CISE CRII proposal titled “CRII: III: RUI: Association Testing and Inversion Detection without Reference Genomes”!

Reference genomes are the backbone (literally) of nearly all existing methods for analyzing genetic variation. Unfortunately, this is sub-optimal. For many non-model species, it is extraordinary difficult to assemble complete genomes. Challenges include difficulties in rearing organisms in the lab to facilitate inbreeding.

Even when reference genomes are available, if the genomes are not assembled from representative samples, it will not be possible to detect all possible variations with that genome. For example, a recent study performed a de novo assembly of reads that did not align to the human reference genome from 910 humans of African descent. The study found a substantial fraction of the new assembly was absent from the standard human reference genome. This has massive ethical implications when reference genomes are used for medical applications.

I proposed adapting my previous methods for detecting inversions from SNPs to k-mers. Based on the work of my group and others, we know that PCA can detect inversions from SNPs. PCA does not take into account the spatial relationships of the SNPs, meaning that it does not in fact need a reference genome. While my previous work was targeted at improving the accuracy of inversion detection with PCA by exploiting spatial information, we will need to develop new ways to perform confident inversion detection for this proposal.

We will demonstrate the utility of our methods through applications to association testing in insect vectors. Due to the number of large inversions in insects, inversion information is often corrected for when doing genome-wide association studies. The methods developed by my team will enable association testing for problems such as identifying the genetic basis of insecticide resistance in non-model insect vectors.

The award will providing funding for salary and travel for me and two students per year for a total of two years.