A draft human pangenome reference

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample

On the Key Role of Composition in Object-Oriented Modelling

The success of object-oriented software modelling depends to a large extent on the ability to create adequate abstractions. While abstraction itself must remain an intellectual process, a modelling language can support or hinder this process by offering different kinds or dimensions of abstraction. For instance, adhering to the object-oriented paradigm UML incorporates classification and generalization as its key abstraction mechanisms. When it comes to taking the complexity out of real systems, however, we argue that classification and generalization alone are ill-suited to produce abstractions that are both manageable and meaningful. As a remedy, we propose to regard composition as an alternative form of abstraction, and find that it naturally comes with properties that are practically needed. We contrast our view of composition with that of it being a special kind of association, with the composition of deployable elements, and with UML's model management constructs such as packaging