In order to provide a comprehensive resource for human structural variants (SVs), we generated long-read sequence data and analyzed SVs for fifteen human genomes. We sequence resolved 99,604 ...insertions, deletions, and inversions including 2,238 (1.6 Mbp) that are shared among all discovery genomes with an additional 13,053 (6.9 Mbp) present in the majority, indicating minor alleles or errors in the reference. Genotyping in 440 additional genomes confirms the most common SVs in unique euchromatin are now sequence resolved. We report a ninefold SV bias toward the last 5 Mbp of human chromosomes with nearly 55% of all VNTRs (variable number of tandem repeats) mapping to this portion of the genome. We identify SVs affecting coding and noncoding regulatory loci improving annotation and interpretation of functional variation. These data provide the framework to construct a canonical human reference and a resource for developing advanced representations capable of capturing allelic diversity.
Display omitted
•We sequence resolve and annotate 99,604 common human structural variants•55% of VNTRs map to the end of chromosomes and correlate with double-strand breaks•Alternate alleles facilitate accurate genotyping with short reads and new associations•We patch the reference and add diversity needed for developing a pan human genome
Long-read sequencing allows generation of a large catalog of human structural variants and the development of an algorithm for genotyping SVs from short-read data, clarifying the spectrum and importance of structural variation in the human genome.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have developed a computational method based on polyploid phasing of long sequence reads to resolve collapsed regions of segmental duplications within genome assemblies. Segmental Duplication ...Assembler (SDA; https://github.com/mvollger/SDA ) constructs graphs in which paralogous sequence variants define the nodes and long-read sequences provide attraction and repulsion edges, enabling the partition and assembly of long reads corresponding to distinct paralogs. We apply it to single-molecule, real-time sequence data from three human genomes and recover 33-79 megabase pairs (Mb) of duplications in which approximately half of the loci are diverged (<99.8%) compared to the reference genome. We show that the corresponding sequence is highly accurate (>99.9%) and that the diverged sequence corresponds to copy-number-variable paralogs that are absent from the human reference genome. Our method can be applied to other complex genomes to resolve the last gene-rich gaps, improve duplicate gene annotation, and better understand copy-number-variant genetic diversity at the base-pair level.
Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length ...complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ~17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors.
Full text
Available for:
BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
As part of the Industry 4.0 movement, the introduction of digital manufacturing technologies (DMTs) poses various concerns, particularly the impact of technology adoption on the workforce. In ...consideration of adoption challenges and implications, various studies explore the topic from the perspective of safety, socio-economic impact, technical readiness, and risk assessment. This paper presents mixed methods research to explore the challenges and acceptance factors of the adoption of human-robot collaboration (HRC) applications and other digital manufacturing technologies from the perspective of different stakeholders: from manufacturing employees at all levels to legal experts to consultants to ethicists. We found that some of the prominent challenges and tensions inherent in technology adoption are job displacement, employee’s acceptance, trust, and privacy. This paper argues that it is crucial to understand the wider human factors implications to better strategize technology adoption; therefore, it recommends interventions targeted at individual employees and at the organisational level. This paper contributes to the roadmap of responsible DMT and HRC implementation to encourage a sustainable workforce in digital manufacturing.
Feedback is valuable for allowing us to improve on tasks. While retrospective feedback can help us improve for next time, feedback ‘in action’ can allow us to improve the outcome of on-going tasks. ...In this article, we use data from functional Near InfraRed Spectroscopy to provide participants with feedback about their mental workload levels
during
high-workload tasks. We evaluate the impact of this feedback on task performance and perceived task performance, in comparison to industry standard mid-task self-assessments, and explore participants’ perceptions of this feedback. In line with previous work, we confirm that deploying self-reporting methods affect both perceived and actual performance. Conversely, we conclude that our objective concurrent feedback correlated more closely with task demand, supported reflection in action, and did not negatively affect performance. Future work, however, should focus on the
design
of this feedback and the potential behaviour changes that will result.
With greater access to computational resources, people use search to address many everyday challenges in their lives, including solving technology problems. Although there are now many useful ...‘how-to’ resources online (especially videos on YouTube), it can still be difficult to identify, understand, and resolve certain kinds of technical problem. While research tasks have been studied for many years and we know the tactics people use, we know far less about searchers’ tactics for how-to technical tasks that involve actually being able to apply found information to resolve a problem. Crucial to our study was developing and studying a highly realistic, how-to technical task, for which there was no single guidance resource: making a phone safe for a child. After providing 39 participants with an actual phone to fix, and a search engine to perform the task, we analysed their search tactics using retrospective cued think aloud interviews. Our primary contribution is a set of 77 tactics used, in three categories, along with detail of how common they were. We conclude that people had a lot of tactics in their repertoire. Although it was not hard for participants to find relevant information, what was hard was for participants to find information they could use; indeed only 23% of participants successfully completed the entire task. Domain knowledge affected the choice of tactics used (although not necessarily towards better task success). We discuss these influences and make design recommendations for how future search systems can support those in resolving how-to technical tasks.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Cognitive training and assessment technologies offer the promise of dementia risk reduction and a more timely diagnosis of dementia, respectively. Cognitive training games may help reduce ...the lifetime risk of dementia by helping to build cognitive reserve, whereas cognitive assessment technologies offer the opportunity for a more convenient approach to early detection or screening.
Objective
This study aims to elicit perspectives of potential end users on factors related to the acceptability of cognitive training games and assessment technologies, including their opinions on the meaningfulness of measurement of cognition, barriers to and facilitators of adoption, motivations to use games, and interrelationships with existing health care infrastructure.
Methods
Four linked workshops were conducted with the same group, each focusing on a specific topic: meaningful improvement, learning and motivation, trust in digital diagnosis, and barriers to technology adoption. Participants in the workshops included local involvement team members acting as facilitators and those recruited via Join Dementia Research through a purposive selection and volunteer sampling method. Group activities were recorded, and transcripts were analyzed using thematic analysis with a combination of a priori and data-driven themes. Using a mixed methods approach, we investigated the relationships between the categories of the Capability, Opportunity, and Motivation–Behavior change model along with data-driven themes by measuring the φ coefficient between coded excerpts and ensuring the reliability of our coding scheme by using independent reviewers and assessing interrater reliability. Finally, we explored these themes and their relationships to address our research objectives.
Results
In addition to discussions around the capability, motivation, and opportunity categories, several important themes emerged during the workshops: family and friends, cognition and mood, work and hobbies, and technology. Group participants mentioned the importance of functional and objective measures of cognitive change, the social aspect of activities as a motivating factor, and the opportunities and potential shortcomings of digital health care provision. Our quantitative results indicated at least moderate agreement on all but one of the coding schemes and good independence of our coding categories. Positive and statistically significant φ coefficients were observed between several coding themes between categories, including a relatively strong positive φ coefficient between capability and cognition (0.468; P<.001).
Conclusions
The implications for researchers and technology developers include assessing how cognitive training and screening pathways would integrate into existing health care systems; however, further work needs to be undertaken to address barriers to adoption and the potential real-world impact of cognitive training and screening technologies.
International Registered Report Identifier (IRRID)
RR2-10.1007/978-3-030-49065-2_4
While efforts to establish best practices with functional near infrared spectroscopy (fNIRS) signal processing have been published, there are still no community standards for applying machine ...learning to fNIRS data. Moreover, the lack of open source benchmarks and standard expectations for reporting means that published works often claim high generalisation capabilities, but with poor practices or missing details in the paper. These issues make it hard to evaluate the performance of models when it comes to choosing them for brain-computer interfaces.
We present an open-source benchmarking framework, BenchNIRS, to establish a best practice machine learning methodology to evaluate models applied to fNIRS data, using five open access datasets for brain-computer interface (BCI) applications. The BenchNIRS framework, using a robust methodology with nested cross-validation, enables researchers to optimise models and evaluate them without bias. The framework also enables us to produce useful metrics and figures to detail the performance of new models for comparison. To demonstrate the utility of the framework, we present a benchmarking of six baseline models linear discriminant analysis (LDA), support-vector machine (SVM), k-nearest neighbours (kNN), artificial neural network (ANN), convolutional neural network (CNN), and long short-term memory (LSTM) on the five datasets and investigate the influence of different factors on the classification performance, including: number of training examples and size of the time window of each fNIRS sample used for classification. We also present results with a sliding window as opposed to simple classification of epochs, and with a personalised approach (within subject data classification) as opposed to a generalised approach (unseen subject data classification).
Results show that the performance is typically lower than the scores often reported in literature, and without great differences between models, highlighting that predicting unseen data remains a difficult task. Our benchmarking framework provides future authors, who are achieving significant high classification scores, with a tool to demonstrate the advances in a comparable way. To complement our framework, we contribute a set of recommendations for methodology decisions and writing papers, when applying machine learning to fNIRS data.
PDF
