SimPEL: Simulation‐based power estimation for sequencing studies of low‐prevalence conditions

Power estimations are important for optimizing genotype‐phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill‐suited for the inherent challenges of studies for low‐prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation‐based program providing power estimations for the design of low‐prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low‐frequency condition studies. SimPEL, as a tool, provides researchers studying low‐frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform‐independent “batteries included” executable and default input files are available at https://github.com/precisionomics/SimPEL .     

Nanomagnetic Modulation of Tumor Redox State

Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe₃O₄ nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day^–1 (compared to 0.58 ± 0.02 day^–1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy.