Local alignment of two-base encoded DNA sequence

<p>Abstract</p> <p>Background</p> <p>DNA sequence comparison is based on optimal local alignment of two sequences using a similarity score. However, some new DNA sequencing technologies do not directly measure the base sequence, but rather an encoded form, such as the two-base encoding considered here. In order to compare such data to a reference sequence, the data must be decoded into sequence. The decoding is deterministic, but the possibility of measurement errors requires searching among all possible error modes and resulting alignments to achieve an optimal balance of fewer errors versus greater sequence similarity.</p> <p>Results</p> <p>We present an extension of the standard dynamic programming method for local alignment, which simultaneously decodes the data and performs the alignment, maximizing a similarity score based on a weighted combination of errors and edits, and allowing an affine gap penalty. We also present simulations that demonstrate the performance characteristics of our two base encoded alignment method and contrast those with standard DNA sequence alignment under the same conditions.</p> <p>Conclusion</p> <p>The new local alignment algorithm for two-base encoded data has substantial power to properly detect and correct measurement errors while identifying underlying sequence variants, and facilitating genome re-sequencing efforts based on this form of sequence data.</p

Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes

Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts’ maps could uncover functionally and clinically related genes.Molecular Psychiatry advance online publication, 31 May 2016; doi:10.1038/mp.2016.84

Towards a History of Mass Violence in the Etat Indépendant du Congo, 1885-1908

The present article provides an up-to-date scholarly introduction to mass violence in the Etat Indépendant du Congo (Congo Free State, EIC). Its aims are twofold: to offer a point of access to the extensive literature and historical debates on the subject, and to make the case for exchanging the currently prevalent top-down narrative, with its excessive focus on King Leopold's character and motives, for one which considers the EIC's culture of violence as a multicausal, broadly based and deeply engrained social phenomenon. The argument is divided into five sections. Following a general outline of the EIC's violent system of administration, I discuss its social and demographic impact (and the controversy which surrounds it) to bring out the need for more regionally focused and context sensitive studies. The dispute surrounding demographics demonstrates that what is fundamentally at stake is the place the EIC's extreme violence should occupy in the history of European ‘modernity’. Since approaches which hinge on Leopoldian exceptionalism are particularly unhelpful in clarifying this issue, I pause to reflect on how such approaches came to dominate the distinct historiographical traditions which emerged in Belgium and abroad before moving on to a more detailed exploration of a selection of causes underlying the EIC's violent nature. While state actors remain in the limelight, I shift the focus from the state as a singular, normative agent, towards the existence of an extremely violent society in which various individuals and social groups within and outside of the state apparatus committed violent acts for multiple reasons. As this argument is pitched at a high level of abstraction, I conclude with a discussion of available source material with which it can be further refined and updated