SUMMARY: Chromosomal copy number aberrations can be efficiently detected and quantified using low-coverage whole-genome sequencing, but analysis is hampered by the lack of knowledge on absolute DNA copy numbers and tumor purity. Here, we describe an analytical tool for Absolute Copy number Estimation, ACE, which scales relative copy number signals from chromosomal segments to optimally fit absolute copy numbers, without the need for additional genetic information, such as SNP data. In doing so, ACE derives an estimate of tumor purity as well. ACE facilitates analysis of large numbers of samples, while maintaining the flexibility to customize models and generate output of single samples. AVAILABILITY AND IMPLEMENTATION: ACE is freely available via www.bioconductor.org and at www.github.com/tgac-vumc/ACE. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Complex designs are common in (observational) clinical studies. Sequencing data for such studies are produced more and more often, implying challenges for the analysis, such as excess of zeros, presence of random effects and multi-parameter inference. Moreover, when sample sizes are small, inference is likely to be too liberal when, in a Bayesian setting, applying a non-appropriate prior or to lack power when not carefully borrowing information across features. RESULTS: We show on microRNA sequencing data from a clinical cancer study how our software ShrinkBayes tackles the aforementioned challenges. In addition, we illustrate its comparatively good performance on multi-parameter inference for groups using a data-based simulation. Finally, in the small sample size setting, we demonstrate its high power and improved FDR estimation by use of Gaussian mixture priors that include a point mass. CONCLUSION: ShrinkBayes is a versatile software package for the analysis of count-based sequencing data, which is particularly useful for studies with small sample sizes or complex designs.