An efficient algorithm for the approximate median selection problem

We present an efficient algorithm for the approximate median selection problem. The algorithm works in-place; it is fast and easy to implement. For a large array it returns, with high probability, a very good estimate of the true median. The running time is linear in the length n of the input. The algorithm performs fewer than 4 1 3n comparisons and 3n exchanges on the average. We present analytical results of the performance of the algorithm, as well as experimental illustrations of its precision. 1

Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3'UTR protect against ALS

The noncoding genome is substantially larger than the protein-coding genome but has been largely unexplored by genetic association studies. Here, we performed region-based rare variant association analysis of >25,000 variants in untranslated regions of 6,139 amyotrophic lateral sclerosis (ALS) whole genomes and the whole genomes of 70,403 non-ALS controls. We identified interleukin-18 receptor accessory protein (IL18RAP) 3′ untranslated region (3′UTR) variants as significantly enriched in non-ALS genomes and associated with a fivefold reduced risk of developing ALS, and this was replicated in an independent cohort. These variants in the IL18RAP 3′UTR reduce mRNA stability and the binding of double-stranded RNA (dsRNA)-binding proteins. Finally, the variants of the IL18RAP 3′UTR confer a survival advantage for motor neurons because they dampen neurotoxicity of human induced pluripotent stem cell (iPSC)-derived microglia bearing an ALS-associated expansion in C9orf72, and this depends on NF-κB signaling. This study reveals genetic variants that protect against ALS by reducing neuroinflammation and emphasizes the importance of noncoding genetic association studies