The Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema was released in 2022 and approved by ISO as a standard for sharing clinical and genomic information about an individual, including phenotypic descriptions, numerical measurements, genetic information, diagnoses, and treatments. A phenopacket can be used as an input file for software that supports phenotype-driven genomic diagnostics and for algorithms that facilitate patient classification and stratification for identifying new diseases and treatments. There has been a great need for a collection of phenopackets to test software pipelines and algorithms. Here, we present Phenopacket Store. Phenopacket Store v.0.1.19 includes 6,668 phenopackets representing 475 Mendelian and chromosomal diseases associated with 423 genes and 3,834 unique pathogenic alleles curated from 959 different publications. This represents the first large-scale collection of case-level, standardized phenotypic information derived from case reports in the literature with detailed descriptions of the clinical data and will be useful for many purposes, including the development and testing of software for prioritizing genes and diseases in diagnostic genomics, machine learning analysis of clinical phenotype data, patient stratification, and genotype-phenotype correlations. This corpus also provides best-practice examples for curating literature-derived data using the GA4GH Phenopacket Schema.

• MeSH
• Algorithms MeSH
• Databases, Genetic MeSH
• Phenotype * MeSH
• Genomics * methods   MeSH
• Humans MeSH
• Software * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The biotransformation of nanoparticles plays a crucial role in determining their biological fate and responses. Although a few engineering strategies (e.g., surface functionalization and shape control) have been employed to regulate the fate of nanoparticles, the genetic control of nanoparticle biotransformation remains an unexplored avenue. Herein, we utilized a CRISPR-based genome-scale knockout approach to identify genes involved in the biotransformation of rare earth oxide (REO) nanoparticles. We found that the biotransformation of REOs in lysosomes could be genetically controlled via SMPD1. Specifically, suppression of SMPD1 inhibited the transformation of La2O3 into sea urchin-shaped structures, thereby protecting against lysosomal damage, proinflammatory cytokine release, pyroptosis and RE-induced pneumoconiosis. Overall, our study provides insight into how to control the biological fate of nanomaterials.

• MeSH
• Biotransformation genetics   MeSH
• CRISPR-Cas Systems MeSH
• Sea Urchins metabolism   MeSH
• Metal Nanoparticles * chemistry   MeSH
• Metals, Rare Earth * metabolism   chemistry   MeSH
• Humans MeSH
• Lysosomes metabolism   MeSH
• Mice MeSH
• Nanoparticles * metabolism   chemistry   MeSH
• Pyroptosis MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci. Here, we present a novel algorithm for extrasensitive and specific variable (V) and joining (J) gene allele inference, allowing the reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput novel allele discovery from a wide variety of existing data sets. The developed algorithm is a part of the MiXCR software. We demonstrate the accuracy of this approach using AIRR-seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) AIRR-seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRA and TRB) AIRR-seq data set, representing 134 individuals. This allowed us to assess the genetic diversity within the IGH, TRA, and TRB loci in different populations and to establish a database of alleles of V and J genes inferred from AIRR-seq data and their population frequencies with free public access through VDJ.online database.

• MeSH
• Alleles * MeSH
• Algorithms * MeSH
• Genetic Variation MeSH
• Humans MeSH
• Receptors, Antigen, B-Cell genetics   immunology   MeSH
• Receptors, Antigen, T-Cell genetics   immunology   MeSH
• Sequence Analysis, DNA methods   MeSH
• Software * MeSH
• High-Throughput Nucleotide Sequencing methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Publikace se zaměřuje na evoluci, lidskou genetiku, na DNA a její použití. Určeno široké veřejnosti.; Kniha velmi přitažlivou formou představuje genetiku.Prezentuje základní principy dědičnosti, vztah genů a prostředí, vliv dědičnosti na nemoci a chování, také popisuje praktické využití poznatků genetiky v medicíně a farmacii nebo v archeologii a kriminalistice včetně identifikace osob. Snaží se odpovědět na otázku, co nám přinesou nové možnosti genetiky a výzkumu DNA a nastiňuje možnosti i hranice genetiky do budoucna.

• MeSH
• Biological Evolution MeSH
• DNA MeSH
• Epigenomics MeSH
• Genetic Engineering MeSH
• Genetic Code * MeSH
• Human Genetics MeSH
• Publication type
• Monograph MeSH
• Popular Work MeSH

• Conspectus
• Obecná genetika. Obecná cytogenetika. Evoluce
• NML Fields
• genetika, lékařská genetika

Single-cell RNA sequencing (scRNA-seq) methods are widely used in life sciences, including immunology. Typical scRNA-seq analysis pipelines quantify the abundance of particular transcripts without accounting for alternative splicing. However, a well-established pan-leukocyte surface marker, CD45, encoded by the PTPRC gene, presents alternatively spliced variants that define different immune cell subsets. Information about some of the splicing patterns in particular cells in the scRNA-seq data can be obtained using isotype-specific DNA oligo-tagged anti-CD45 antibodies. However, this requires generation of an additional sequencing DNA library. Here, we present IDEIS, an easy-to-use software for CD45 isoform quantification that uses single-cell transcriptomic data as the input. We showed that IDEIS accurately identifies canonical human CD45 isoforms in datasets generated by 10× Genomics 5' sequencing assays. Moreover, we used IDEIS to determine the specificity of the Ptprc splicing pattern in mouse leukocyte subsets.

• MeSH
• Alternative Splicing MeSH
• Single-Cell Analysis methods   MeSH
• Leukocyte Common Antigens * genetics   metabolism   MeSH
• Leukocytes metabolism   immunology   MeSH
• Humans MeSH
• Mice MeSH
• Protein Isoforms genetics   MeSH
• Sequence Analysis, RNA methods   MeSH
• Software * MeSH
• Gene Expression Profiling methods   MeSH
• Transcriptome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

We explored how a simple retrovirus, Mason-Pfizer monkey virus (M-PMV) to facilitate its replication process, utilizes DHX15, a cellular RNA helicase, typically engaged in RNA processing. Through advanced genetic engineering techniques, we showed that M-PMV recruits DHX15 by mimicking cellular mechanisms, relocating it from the nucleus to the cytoplasm to aid in viral assembly. This interaction is essential for the correct packaging of the viral genome and critical for its infectivity. Our findings offer unique insights into the mechanisms of viral manipulation of host cellular processes, highlighting a sophisticated strategy that viruses employ to leverage cellular machinery for their replication. This study adds valuable knowledge to the understanding of viral-host interactions but also suggests a common evolutionary history between cellular processes and viral mechanisms. This finding opens a unique perspective on the export mechanism of intron-retaining mRNAs in the packaging of viral genetic information and potentially develop ways to stop it.

• MeSH
• Cell Nucleus metabolism   virology   MeSH
• DEAD-box RNA Helicases metabolism   genetics   MeSH
• Genome, Viral MeSH
• HEK293 Cells MeSH
• Humans MeSH
• Mason-Pfizer monkey virus * genetics   metabolism   physiology   MeSH
• Virus Replication genetics   physiology   MeSH
• RNA, Viral * metabolism   genetics   MeSH
• RNA Helicases metabolism   genetics   MeSH
• Virus Assembly * genetics   physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Recent advances in AI-based methods have revolutionized the field of structural biology. Concomitantly, high-throughput sequencing and functional genomics have generated genetic variants at an unprecedented scale. However, efficient tools and resources are needed to link disparate data types-to 'map' variants onto protein structures, to better understand how the variation causes disease, and thereby design therapeutics. Here we present the Genomics 2 Proteins portal ( https://g2p.broadinstitute.org/ ): a human proteome-wide resource that maps 20,076,998 genetic variants onto 42,413 protein sequences and 77,923 structures, with a comprehensive set of structural and functional features. Additionally, the Genomics 2 Proteins portal allows users to interactively upload protein residue-wise annotations (for example, variants and scores) as well as the protein structure beyond databases to establish the connection between genomics to proteins. The portal serves as an easy-to-use discovery tool for researchers and scientists to hypothesize the structure-function relationship between natural or synthetic variations and their molecular phenotypes.

• MeSH
• Databases, Protein * MeSH
• Genetic Variation MeSH
• Genetic Testing methods   MeSH
• Genomics * methods   MeSH
• Protein Conformation MeSH
• Humans MeSH
• Proteins genetics   chemistry   MeSH
• Proteome genetics   MeSH
• Amino Acid Sequence MeSH
• Software MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

CRISPR/Cas technology is a powerful tool for genome engineering in Aspergillus oryzae as an industrially important filamentous fungus. Previous study has reported the application of the CRISPR/Cpf1 system based on the Cpf1 (LbCpf1) from Lachnospiraceae bacterium in A. oryzae. However, multiplex gene editing have not been investigated using this system. Here, we presented a new CRISPR/Cpf1 multiplex gene editing system in A. oryzae, which contains the Cpf1 nuclease (FnCpf1) from Francisella tularensis subsp. novicida U112 and CRISPR-RNA expression cassette. The crRNA cassette consisted of direct repeats and guide sequences driven by the A. oryzae U6 promoter and U6 terminator. Using the constructed FnCpf1 gene editing system, the wA and pyrG genes were mutated successfully. Furthermore, simultaneous editing of wA and pyrG genes in A. oryzae was performed using two guide sequences targeting these gene loci in a single crRNA array. This promising CRISPR/Cpf1 genome-editing system provides a powerful tool for genetically engineering A. oryzae.

• MeSH
• Aspergillus oryzae * genetics   MeSH
• Gene Editing MeSH
• Francisella * MeSH
• RNA, Guide, CRISPR-Cas Systems MeSH
• Publication type
• Journal Article MeSH

Genome-wide association studies (GWASs) have been successful at finding associations between genetic variants and human traits, including the immune-mediated diseases (IMDs). However, the requirement of large sample sizes for discovery poses a challenge for learning about less common diseases, where increasing volunteer numbers might not be feasible. An example of this is myositis (or idiopathic inflammatory myopathies [IIM]s), a group of rare, heterogeneous autoimmune diseases affecting skeletal muscle and other organs, severely impairing life quality. Here, we applied a feature engineering method to borrow information from larger IMD GWASs to find new genetic associations with IIM and its subgroups. Combining this approach with two clustering methods, we found 17 IMDs genetically close to IIM, including some common comorbid conditions, such as systemic sclerosis and Sjögren's syndrome, as well as hypo- and hyperthyroidism. All IIM subtypes were genetically similar within this framework. Next, we colocalized IIM signals that overlapped IMD signals, and found seven potentially novel myositis associations mapped to immune-related genes, including BLK, IRF5/TNPO3, and ITK/HAVCR2, implicating a role for both B and T cells in IIM. This work proposes a new paradigm of genetic discovery in rarer diseases by leveraging information from more common IMD, and can be expanded to other conditions and traits beyond IMD.

• MeSH
• Autoimmune Diseases genetics   immunology   MeSH
• Genome-Wide Association Study * MeSH
• Genetic Predisposition to Disease * MeSH
• Polymorphism, Single Nucleotide MeSH
• Humans MeSH
• Myositis * genetics   immunology   MeSH
• Immune System Diseases genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Micronutrient deficiency conditions, such as anemia, are the most prevalent global health problem due to inadequate iron and folate in dietary sources. Biofortification advancements can propel the rapid amelioration of nutritionally beneficial components in crops that are required to combat the adverse effects of micronutrient deficiencies on human health. To date, several strategies have been proposed to increase micronutrients in plants to improve food quality, but very few approaches have intrigued `clustered regularly interspaced short palindromic repeats' (CRISPR) modules for the enhancement of iron and folate concentration in the edible parts of plants. In this review, we discuss two important approaches to simultaneously enhance the bioavailability of iron and folate concentrations in rice endosperms by utilizing advanced CRISPR-Cas9-based technology. This includes the 'tuning of cis-elements' and 'enhancer re-shuffling' in the regulatory components of genes that play a vital role in iron and folate biosynthesis/transportation pathways. In particular, base-editing and enhancer re-installation in native promoters of selected genes can lead to enhanced accumulation of iron and folate levels in the rice endosperm. The re-distribution of micronutrients in specific plant organs can be made possible using the above-mentioned contemporary approaches. Overall, the present review discusses the possible approaches for synchronized iron and folate biofortification through modification in regulatory gene circuits employing CRISPR-Cas9 technology.

• MeSH
• Biofortification * MeSH
• CRISPR-Cas Systems * MeSH
• Gene Editing methods   MeSH
• Plants, Genetically Modified * metabolism   genetics   MeSH
• Folic Acid * metabolism   MeSH
• Humans MeSH
• Oryza metabolism   genetics   MeSH
• Iron * metabolism   MeSH
• Crops, Agricultural * metabolism   genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH