Sequence alignment underpins all of comparative genomics, yet it remains an incompletely solved problem. In particular, the statistical uncertainty within inferred alignments is often disregarded, while parametric or phylogenetic inferences are considered meaningless without confidence estimates. Here, we report on a theoretical and simulation study of pairwise alignments of genomic DNA at human-mouse divergence. We find that >15% of aligned bases are incorrect in existing whole-genome alignments, and we identify three types of alignment error, each leading to systematic biases in all algorithms considered. Careful modeling of the evolutionary process improves alignment quality; however, these improvements are modest compared with the remaining alignment errors, even with exact knowledge of the evolutionary model, emphasizing the need for statistical approaches to account for uncertainty. We develop a new algorithm, Marginalized Posterior Decoding (MPD), which explicitly accounts for uncertainties, is less biased and more accurate than other algorithms we consider, and reduces the proportion of misaligned bases by a third compared with the best existing algorithm. To our knowledge, this is the first nonheuristic algorithm for DNA sequence alignment to show robust improvements over the classic Needleman-Wunsch algorithm. Despite this, considerable uncertainty remains even in the improved alignments. We conclude that a probabilistic treatment is essential, both to improve alignment quality and to quantify the remaining uncertainty. This is becoming increasingly relevant with the growing appreciation of the importance of noncoding DNA, whose study relies heavily on alignments. Alignment errors are inevitable, and should be considered when drawing conclusions from alignments. Software and alignments to assist researchers in doing this are provided at

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This article report the measurements on-board a small aircraft at the same altitude and around the same geographic coordinates. The measurements of Ambient Dose Equivalent Rate (H*(10)) were performed in several positions inside the aircraft, close and far from the pilot location and the discrimination between neutron and non-neutron components. The results show that the neutrons are attenuated close to fuel depots and the non-neutron component appears to have the opposite behavior inside the aircraft. These experimental results are also confronted with results from Monte Carlo simulation, obtained with the MCNPX code, using a simplified model of the Learjet-type aircraft and a modeling of the standard atmosphere, which reproduces the real energy and angular distribution of the particles. The Monte Carlo simulation agreed with the experimental measurements and shows that the total H*(10) presents small variation (around 1%) between the positions inside aircraft, although the neutron spectra present significant variations.

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