Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

Ethics of Infection Control Measures for Carriers of Antimicrobial Drug–Resistant Organisms

Contains fulltext : 195137.pdf (publisher's version ) (Open Access

Infection control measures in times of antimicrobial resistance: a matter of solidarity.

Control measures directed at carriers of multidrug-resistant organisms are traditionally approached as a trade-off between public interests on the one hand and individual autonomy on the other. We propose to reframe the ethical issue and consider control measures directed at carriers an issue of solidarity. Rather than asking "whether it is justified to impose strict measures", we propose asking "how to best care for a person's carriership and well-being in ways that do not imply an unacceptable risk for others?". A solidarity approach could include elevating baseline levels of precaution measures and accepting certain risks in cases where there is exceptionally much at stake. A generous national compensation policy that also covers for costs related to dedicated care is essential in a solidarity approach. An additional benefit of reframing the questions is that it helps to better acknowledge that being subjected to control measures is a highly personal matter.</p

Near threshold production of η-mesons in proton neutron collisions at ANKE

The interaction between hadrons and η-mesons is an intensively studied topic. Due to its stength it might lead to the formation of η-mesic nuclei. In order to study the characteristics of this interaction a measurement of the reaction p + d → d + η + psp has been performed at the ANKE spectrometer at the COSY accelerator of the Forschungszentrum Jülich. The two different beam momenta (p1 = 2.09 GeV/c and p2 = 2.25 GeV/c) in combination with the Fermi motion inside the target deuteron grant access to the determination of total and differential cross sections in an excess energy range from threshold up to Q = 90 MeV. While the course of the total cross section, especially near threshold, will allow to extract the scattering length adη via an s-wave final state interaction ansatz, the differential cross sections permit to verify the legitimacy of the s-wave assumption

Near threshold production of η-mesons in proton neutron collisions at ANKE

The interaction between hadrons and η-mesons is an intensively studied topic. Due to its stength it might lead to the formation of η-mesic nuclei. In order to study the characteristics of this interaction a measurement of the reaction p + d → d + η + psp has been performed at the ANKE spectrometer at the COSY accelerator of the Forschungszentrum Jülich. The two different beam momenta (p1 = 2.09 GeV/c and p2 = 2.25 GeV/c) in combination with the Fermi motion inside the target deuteron grant access to the determination of total and differential cross sections in an excess energy range from threshold up to Q = 90 MeV. While the course of the total cross section, especially near threshold, will allow to extract the scattering length adη via an s-wave final state interaction ansatz, the differential cross sections permit to verify the legitimacy of the s-wave assumption

Moleculaire typeringstechnieken in de bron- en contactopsporing: 9 ethische vragen om de besluitvorming te structureren

In dit onderzoek wordt een serie van 9 vragen gepresenteerd die gebruikt kunnen worden om de besluitvorming rondom het gebruik van moleculaire typeringstechniek voor de bron- en contactopsporing te structureren. De vragen zelf leiden niet tot een keuze, maar moeten worden gezien als een instrument dat het besluitvormingsproces structureert. De set vragen is bedoeld voor professionals werkzaam bij GGD, RIVM of medisch microbiologisch laboratoria

Moleculaire typeringstechnieken in de bron- en contactopsporing: 9 ethische vragen om de besluitvorming te structureren

In dit onderzoek wordt een serie van 9 vragen gepresenteerd die gebruikt kunnen worden om de besluitvorming rondom het gebruik van moleculaire typeringstechniek voor de bron- en contactopsporing te structureren. De vragen zelf leiden niet tot een keuze, maar moeten worden gezien als een instrument dat het besluitvormingsproces structureert. De set vragen is bedoeld voor professionals werkzaam bij GGD, RIVM of medisch microbiologisch laboratoria

Loss of ADAM17 is associated with severe multiorgan dysfunction

ADAM metallopeptidase domain 17 (ADAM17) is responsible for processing large numbers of proteins. Recently, 1 family involving 2 patients with a homozygous mutation in ADAM17 were described, presenting with skin lesions and diarrhea. In this report, we describe a second family confirming the existence of this syndrome. The proband presented with severe diarrhea, skin rash, and recurrent sepsis, eventually leading to her death at the age of 10 months. We performed exome sequencing and detailed pathological and immunological investigations. We identified a novel homozygous frameshift mutation in ADAM17 (NM_003183.4:c.308dupA) leading to a premature stop codon. CD4(+) and CD8(+) T-cell stimulation assays showed severely diminished tumor necrosis factor-α and interleukin-2 production. Skin biopsies indicated a focal neutrophilic infiltrate and spongiotic dermatitis. Interestingly, the patient developed unexplained systolic hypertension and nonspecific hepatitis with apoptosis. This report provides evidence for an important role of ADAM17 in human immunological response and underscores its multiorgan involvement