The human genome is diploid, which requires assigning heterozygous single nucleotide polymorphisms (SNPs) to the two copies of the genome. The resulting haplotypes, lists of SNPs belonging to each copy, are crucial for downstream analyses in population genetics. Currently, statistical approaches, which are oblivious to direct read information, constitute the state-of-the-art. Haplotype assembly, which addresses phasing directly from sequencing reads, suffers from the fact that sequencing reads of the current generation are too short to serve the purposes of genome-wide phasing. While future-technology sequencing reads will contain sufficient amounts of SNPs per read for phasing, they are also likely to suffer from higher sequencing error rates. Currently, no haplotype assembly approaches exist that allow for taking both increasing read length and sequencing error information into account. Here, we suggest WhatsHap, the first approach that yields provably optimal solutions to the weighted minimum error correction problem in runtime linear in the number of SNPs. WhatsHap is a fixed parameter tractable (FPT) approach with coverage as the parameter. We demonstrate that WhatsHap can handle datasets of coverage up to 203, and that 153 are generally enough for reliably phasing long reads, even at significantly elevated sequencing error rates. We also find that the switch and flip error rates of the haplotypes we output are favorable when comparing them with state-of-the-art statistical phasers.

Read-based phasing allows to reconstruct the haplotype structure of a sample purely from sequencing reads. While phasing is a required step for answering questions about population genetics, compound heterozygosity, and to aid in clinical decision making, there has been a lack of an accurate, usable and standards-based software.WhatsHap is a production-ready tool for highly accurate read-based phasing. It was designed from the beginning to leverage third-generation sequencing technologies, whose long reads can span many variants and are therefore ideal for phasing. WhatsHap works also well with second-generation data, is easy to use and will phase not only SNVs, but also indels and other variants. It is unique in its ability to combine read-based with genetic phasing, allowing to further improve accuracy if multiple related samples are provided.

Spatial acuity of the touch sense and its variation in aging came under psychophysical scrutiny at the fingertip and control body sites. Acuity is viewed as encompassing the discrimination of four features of simple stimulus configurations: (11) discontinuity (gaps in lines or disks), (2) locus on the skin, (3) length (or area), and (4) orientation (e.g., along or across the finger). Each of these dimensions of acuity serves uniquely in tactile perception, as illustrated in the structure of braille. For their measurement, psychophysical tests were developed and refined. These were aimed at freedom from bias, rapid estimation of acuity thresholds in hundreds of subjects, and eventual applicability to the whole body surface. Some 14 versions of the tests were administered in three experiments, yielding 1478 individual thresholds. Experiment I (15 young and 15 elderly subjects) and Experiment II (131 subjects, ages 18 to 87 years) shed light on the nature of discrimination of discontiniuty and orientation. These mainly concern pitfalls of measurement and influence of exact stimulus configuration. Experiment III (115 subjects, ages 8 to 86 years) examined refined versions of tests for all four dimensions of acuity. Four principal findings emerged: (1) At all ages, thresholds for the four dimensions of acuity differ from one another in size--in order from smallest to largest: length, locus, orientation, and discontinuity. Exact sizes differ for transverse and longitudinal stimulus alignment. (2) All four acuity dimensions deteriorate with age, to a first approximation manifesting a constant increase in threshold of approximately 1% per annum between ages 20 and 80 years. That similar rates of deterioration characterize all four dimensions in the fingertip suggests a common mechanism, possibly thinning of the same mediating receptor network. (3) Acuity at more central sites (forearm, lip) deteriorates more slowly than at the fingertip. (4) Individual differences in acuity abound, even after the effects of aging are discounted.