Regulation of Network Interactions of Personnel Training for SPE

В статье поднимаются вопросы нормотворчества при разработке локальных нормативных актов. Приводится пример разработки регламента сетевого взаимодействия из опыта Российского государственного профессионально-педагогического университета.The article raises questions of rule-making in the development of local regulations. An example of the development of a network interaction regulation from the experience of the Russian State Vocational Pedagogical University is given

Outcomes for 18 to 25-year-olds with borderline personality disorder in a dedicated young adult only DBT programme compared to a general adult DBT programme for all ages 18

Aim Targeting young adults with borderline personality disorder (BPD) for treatment may carry significant social and clinical benefits. We aimed to evaluate a community‐based Dialectical Behaviour Therapy (DBT) programme delivered exclusively to young adults with BPD. Methods We describe a naturally occurring non‐equivalent, quasi‐experimental comparison of outcomes for young adults (18‐25 years) with BPD following 1 year of treatment in either a young adult only DBT programme or a general adult DBT programme (18+ years). Twenty‐four young adults enrolled in a community‐based young adult DBT programme open only to 18‐ to 25‐year‐olds with BPD. Another 13 young adults, also 18‐25 years, enrolled in a general adult DBT programme open to all ages above 18 years. Both treatment conditions offered all modes of standard DBT for 1 year. Participants completed a battery of self‐report measures on mental health symptoms at baseline and again at treatment completion after 1 year. Discharge rates at 2 years post‐treatment completion were also recorded. Results Better outcomes were found on borderline symptom severity and general psychopathology among completers of young adult DBT, with a large effect size for treatment condition as well as greater clinically significant change. Discharge rates from mental health services 24 months later were also higher for completers of young adult DBT. Conclusions There may be advantages in delivering DBT to young adults in an age‐specific programme, possibly due to group cohesion. Methodological limitations apply, such as small sample size and non‐randomization. Further controlled research is needed

Alternate-locus aware variant calling in whole genome sequencing

BACKGROUND: The last two human genome assemblies have extended the previous linear golden-path paradigm of the human genome to a graph-like model to better represent regions with a high degree of structural variability. The new model offers opportunities to improve the technical validity of variant calling in whole-genome sequencing (WGS). METHODS: We developed an algorithm that analyzes the patterns of variant calls in the 178 structurally variable regions of the GRCh38 genome assembly, and infers whether a given sample is most likely to contain sequences from the primary assembly, an alternate locus, or their heterozygous combination at each of these 178 regions. We investigate 121 in-house WGS datasets that have been aligned to the GRCh37 and GRCh38 assemblies. RESULTS: We show that stretches of sequences that are largely but not entirely identical between the primary assembly and an alternate locus can result in multiple variant calls against regions of the primary assembly. In WGS analysis, this results in characteristic and recognizable patterns of variant calls at positions that we term alignable scaffold-discrepant positions (ASDPs). In 121 in-house genomes, on average 51.8±3.8 of the 178 regions were found to correspond best to an alternate locus rather than the primary assembly sequence, and filtering these genomes with our algorithm led to the identification of 7863 variant calls per genome that colocalized with ASDPs. Additionally, we found that 437 of 791 genome-wide association study hits located within one of the regions corresponded to ASDPs. CONCLUSIONS: Our algorithm uses the information contained in the 178 structurally variable regions of the GRCh38 genome assembly to avoid spurious variant calls in cases where samples contain an alternate locus rather than the corresponding segment of the primary assembly. These results suggest the great potential of fully incorporating the resources of graph-like genome assemblies into variant calling, but also underscore the importance of developing computational resources that will allow a full reconstruction of the genotype in personal genomes. Our algorithm is freely available at https://github.com/charite/asdpex. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-016-0383-z) contains supplementary material, which is available to authorized users

Nanopore sequencing and assembly of a human genome with ultra-long reads

We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ~30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ~3 Mb). Next, we developed a protocol to generate ultra-long reads (N50 > 100kb, up to 882 kb). Incorporating an additional 5×-coverage of these data more than doubled the assembly contiguity (NG50 ~6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4 Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length and closure of gaps in the reference human genome assembly GRCh38

Epigenetic engineering shows that a human centromere resists silencing mediated by H3K27me3/K9me3

Centromeres are characterized by the centromere-specific H3 variant CENP-A, which is embedded in chromatin with a pattern characteristic of active transcription that is required for centromere identity. It is unclear how centromeres remain transcriptionally active despite being flanked by repressive pericentric heterochromatin. To further understand centrochromatin’s response to repressive signals, we nucleated a Polycomb-like chromatin state within the centromere of a human artificial chromosome (HAC) by tethering the methyltransferase EZH2. This led to deposition of the H3K27me3 mark and PRC1 repressor binding. Surprisingly, this state did not abolish HAC centromere function or transcription, and this apparent resistance was not observed on a noncentromeric locus, where transcription was silenced. Directly tethering the reader/repressor PRC1 bypassed this resistance, inactivating the centromere. We observed analogous responses when tethering the heterochromatin Editor Suv39h1-methyltransferase domain (centromere resistance) or reader HP1α (centromere inactivation), respectively. Our results reveal that the HAC centromere can resist repressive pathways driven by H3K9me3/H3K27me3 and may help to explain how centromeres are able to resist inactivation by flanking heterochromatin

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

Scenario-Based Performance Engineering with UCMNAV

The analysis of a scenario specification for a new system can address some questions of system performance, in the sense of delay and capacity estimation