https://www.selleckchem.com/products/folinic-acid.html Daily temporal trends analysed in the context of circadian rhythms reveal alterations in amplitude and phase of diurnal patterns of autonomic balance. Further analysis by genotype class confirms a graded presentation of the Rett syndrome phenotype such that patients with early truncating mutations were most different from controls, while late truncating and missense mutations were least different from controls. CONCLUSIONS Comprehensive autonomic measures from extensive inhome physiological measurements can detect subtle variations in the phenotype of girls with Rett syndrome, suggesting these techniques are suitable for guiding novel therapies. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Accurate massively parallel sequencing (MPS) of genetic variants is key to many areas of science and medicine, such as cataloging population genetic variation and diagnosing genetic diseases. Certain genomic positions can be prone to higher rates of systematic sequencing and alignment bias that limit accuracy, resulting in false positive variant calls. Current standard practices to differentiate between loci that can and cannot be sequenced with high confidence utilize consensus between different sequencing methods as a proxy for sequencing confidence. These practices have significant limitations, and alternative methods are required to overcome them. We have developed a novel statistical method based on summarizing sequenced reads from whole-genome clinical samples and cataloging them in "Incremental Databases" that maintain individual confidentiality. Allele statistics were cataloged for each genomic position that consistently showed systematic biases with the corresponding MPS sequencing pipeline. We found systematic biases present at ∼1%-3% of the human autosomal genome across five patient cohorts. We identified which genomic regions were more or less prone to