Comparison of Different Organometallics Towards Electrophilic Aromatic At-Astatinations of Highly Reactive Tetrazines.

Organometallics can be used as precursors for electrophilic At-statinations. In this report, we compared the potential of aryl trimethylsilanes, -germanes, or -stannanes to be used as precursors to At-label highly reactive tetrazines. Tetrazines can be used for pretargeted radioligand therapies or be applied as synthons to radiolabel rapidly and orthogonally a broad set of precursors such as peptides, mAbs or nanomedicines.

Multiplexed chromatin immunoprecipitation sequencing for quantitative study of histone modifications and chromatin factors.

ChIP-seq is a widely used technique for studying histone post-translational modifications and DNA-binding proteins. DNA fragments associated with a specific protein or histone modification epitope are captured by using antibodies, sequenced and mapped to a reference genome. Albeit versatile and popular, performing many parallel ChIP-seq experiments to compare different conditions, replicates and epitopes is laborious, is prone to experimental variation and does not allow quantitative comparisons unless adequate spike-in chromatin is included.

Designing efficient randstrobes for sequence similarity analyses.

Motivation: Substrings of length k, commonly referred to as k-mers, play a vital role in sequence analysis. However, k-mers are limited to exact matches between sequences leading to alternative constructs. We recently introduced a class of new constructs, strobemers, that can match across substitutions and smaller insertions and deletions.

[Lu]Lu-DOTAGA.Glu.(FAPi) Radionuclide Therapy: a New Treatment Option for Patients with Glioblastoma Multiforme.

In this case report, we present the clinical management of a 52-year-old female patient with a recurrent right temporo-parietal glioblastoma multiforme (GBM). The patient presented with symptoms of headache and loss of balance and recurrence on magnetic resonance imaging (MRI). To evaluate the fibroblast activation protein inhibitor (FAPi) expression in the recurrent lesion, an exploratory [ Ga]Ga-DOTA.

BLR: a flexible pipeline for haplotype analysis of multiple linked-read technologies.

Linked-read sequencing promises a one-method approach for genome-wide insights including single nucleotide variants (SNVs), structural variants, and haplotyping. We introduce Barcode Linked Reads (BLR), an open-source haplotyping pipeline capable of handling millions of barcodes and data from multiple linked-read technologies including DBS, 10× Genomics, TELL-seq and stLFR. Running BLR on DBS linked-reads yielded megabase-scale phasing with low (<0.

Therapeutic potential of [Lu]Lu-DOTAGA-FAPi dimers in metastatic breast cancer patients with limited treatment options: efficacy and safety assessment.

Purpose: The upregulation of fibroblast activation protein (FAP) expression has been observed in various cancers, including metastatic breast carcinoma, prompting research into small molecule inhibitors for both diagnostic and therapeutic purposes. While the diagnostic value of PET/CT imaging using  Ga- or F-labelled FAPi-monomers in breast cancer diagnosis is well-established, there is a significant need for therapeutic analogs. This retrospective study aimed to assess the safety and effectiveness of [Lu]Lu-DOTAGA.

Head-to-head comparison of [Ga]Ga-DOTA.SA.FAPi with [F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers.

Purpose: In the context of radioiodine-resistant follicular-cell derived thyroid cancers (RAI-R-FCTC), [F]F-FDG PET/CT serves as a widely used and valuable diagnostic imaging method. However, there is growing interest in utilizing molecular imaging probes that target cancer-associated fibroblasts (CAFs) as an alternative approach. This study sought to compare the diagnostic capabilities of [Ga]Ga-DOTA.

Head-to-Head Comparison of [Ga]Ga-DOTA.SA.FAPi and [Ga]Ga-DOTANOC Positron Emission Tomography/Computed Tomography Imaging for the Follow-Up Surveillance of Patients with Medullary Thyroid Cancer.

A theranostic probe for accurate staging and treatment is crucial for the management of medullary thyroid cancers (MTCs). The abundance of stroma in most of thyroid cancers, including MTC, opens new avenues for selecting cancer-associated fibroblasts (CAFs) as new molecular imaging and therapeutic targets. [Ga]Ga-labeled fibroblast activation protein inhibitor (FAPi) molecules have gained importance as alternative molecular imaging agents in the imaging of thyroid cancers.

Head-to-Head Comparison between [Ga]Ga-DOTA.SA.FAPi and [F]F-FDG PET/CT Imaging in Patients with Breast Cancer.

This study aimed to compare the diagnostic performance of [Ga]Ga-DOTA.SA.FAPi with that of [F]F-FDG PET/CT in detecting primary and metastatic lesions of breast cancer.

Novel Generation of FAP Inhibitor-Based Homodimers for Improved Application in Radiotheranostics.

Radiopharmaceuticals based on the highly potent FAP inhibitor (FAPi) UAMC-1110 have shown great potential in molecular imaging, but the short tumor retention time of the monomers do not match the physical half-lives of the important therapeutic radionuclides Lu and Ac. This was improved with the dimer DOTAGA.(SA.

Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics.

The mammalian brain contains many specialized cells that develop from a thin sheet of neuroepithelial progenitor cells. Single-cell transcriptomics revealed hundreds of molecularly diverse cell types in the nervous system, but the lineage relationships between mature cell types and progenitor cells are not well understood. Here we show in vivo barcoding of early progenitors to simultaneously profile cell phenotypes and clonal relations in the mouse brain using single-cell and spatial transcriptomics.

Characterizing robotic surgical expertise: An exploratory study of neural activation during mental imagery of robotic suturing.

Background: Mental imagery (MI) aids skill acquisition, however, it is unclear to what extend MI is used by experienced surgeons. The purpose of this study was to assess differences in MI of participants with varying surgical expertise in robotic surgery.

Methods: Students, residents, and surgeons completed the Mental Imagery Questionnaire to assess MI for robotic suturing.

Sarek: A portable workflow for whole-genome sequencing analysis of germline and somatic variants.

Whole-genome sequencing (WGS) is a fundamental technology for research to advance precision medicine, but the limited availability of portable and user-friendly workflows for WGS analyses poses a major challenge for many research groups and hampers scientific progress. Here we present Sarek, an open-source workflow to detect germline variants and somatic mutations based on sequencing data from WGS, whole-exome sequencing (WES), or gene panels. Sarek features (i) easy installation, (ii) robust portability across different computer environments, (iii) comprehensive documentation, (iv) transparent and easy-to-read code, and (v) extensive quality metrics reporting.

Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses.

Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs).

From cytogenetics to cytogenomics: whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability.

Background: Since different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.

Methods: We analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n = 68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n = 156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.

High-Quality Library Preparation for NGS-Based Immunoglobulin Germline Gene Inference and Repertoire Expression Analysis.

Next generation sequencing (NGS) of immunoglobulin (Ig) repertoires (Rep-seq) enables examination of the adaptive immune system at an unprecedented level. Applications include studies of expressed repertoires, gene usage, somatic hypermutation levels, Ig lineage tracing and identification of genetic variation within the Ig loci through inference methods. All these applications require starting libraries that allow the generation of sequence data with low error rate and optimal representation of the expressed repertoire.

De Novo Assembly of Two Swedish Genomes Reveals Missing Segments from the Human GRCh38 Reference and Improves Variant Calling of Population-Scale Sequencing Data.

The current human reference sequence (GRCh38) is a foundation for large-scale sequencing projects. However, recent studies have suggested that GRCh38 may be incomplete and give a suboptimal representation of specific population groups. Here, we performed a de novo assembly of two Swedish genomes that revealed over 10 Mb of sequences absent from the human GRCh38 reference in each individual.

Corrigendum: Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.

This corrects the article DOI: 10.1038/nature18614.

Atropos: specific, sensitive, and speedy trimming of sequencing reads.

A key step in the transformation of raw sequencing reads into biological insights is the trimming of adapter sequences and low-quality bases. Read trimming has been shown to increase the quality and reliability while decreasing the computational requirements of downstream analyses. Many read trimming software tools are available; however, no tool simultaneously provides the accuracy, computational efficiency, and feature set required to handle the types and volumes of data generated in modern sequencing-based experiments.

SweGen: a whole-genome data resource of genetic variability in a cross-section of the Swedish population.

Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry.

Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity.

Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%.

Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.

Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells and a significant increase in cardiomyocyte numbers. Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location.

Read-based phasing of related individuals.

Motivation: Read-based phasing deduces the haplotypes of an individual from sequencing reads that cover multiple variants, while genetic phasing takes only genotypes as input and applies the rules of Mendelian inheritance to infer haplotypes within a pedigree of individuals. Combining both into an approach that uses these two independent sources of information-reads and pedigree-has the potential to deliver results better than each individually.

Results: We provide a theoretical framework combining read-based phasing with genetic haplotyping, and describe a fixed-parameter algorithm and its implementation for finding an optimal solution.