Large Sequence Research Articles

Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua

Abstract Lonicera japonica is a well-known medicinal plant, and the Damaohua cultivar is one of the oldest known honeysuckle cultivars in China. The 155,151 bp chloroplast genome of this cultivar was obtained through Illumina sequencing. The genome includes a pair of inverted repeats (IRa and IRb; 23,789 bp each), a large single-copy region (88,924 bp), and a small single-copy (SSC) region (18,649 bp). In total, 127 unique genes were identified: 80 protein-coding, 39 tRNA, and 8 rRNA genes. Only ycf3 contained two introns. Eighty-nine large repetitive sequences and 54 simple sequence repeats were detected. Fifty potential RNA editing sites were predicted. Adaptive evolution analysis revealed that infA, matK, petB, petD, rbcL, rpl16, rpl2, rps3, ycf1, and ycf2 were positively selected, possibly reflecting the specific environmental adaptations of this cultivar. Sequence alignment and analysis revealed several candidate fragments for Lonicera species identification, such as the intergenic regions rpoB-petN, rbcL-accD, and psaA-ycf3. The IR region boundary and phylogenetic analysis revealed that the L. japonica cv. Damaohua chloroplast genome was most closely related to the L. japonica genome, but there were five distinct differences between the two. There are four sites with high variability between L. japonica and L. japonica cv. Damaohua with nucleotide variability (Pi) greater than 0.002, including rps2-rpoC2, atpB-rbcL, ycf1, and ycf1-trnN GUU. The differences between L. japonica and L. japonica cv. Damaohua were further confirmed by the single nucleotide polymorphism sites between these two species. Therefore, this study revealed that the chloroplast genome can serve as a universal super barcode for plant identification, which can identify differences and help distinguish Lonicera japonica from related species. An understanding of Lonicera japonica cv. Damaohua chloroplast genomics and a comparative analysis of Lonicera species will provide a scientific basis for breeding, species identification, systematic evolution analysis, and chloroplast genetic engineering research on medicinal honeysuckle plants.

Beyond bigrams: call sequencing in the common marmoset (Callithrix jacchus) vocal system.

Over the last two decades, an emerging body of research has demonstrated that non-human animals exhibit the ability to combine context-specific calls into larger sequences. These structures have frequently been compared with language's syntax, whereby linguistic units are combined to form larger structures, and leveraged to argue that syntax might not be unique to language. Currently, however, the overwhelming majority of examples of call combinations are limited to simple sequences comprising just two calls which differ dramatically from the open-ended hierarchical structuring of the syntax found in language. We revisit this issue by taking a whole-repertoire approach to investigate combinatoriality in common marmosets (Callithrix jacchus). We use Markov chain models to quantify the vocal sequences produced by marmosets providing evidence for structures beyond the bigram, including three-call and even combinations of up to eight or nine calls. Our analyses of these longer vocal sequences are suggestive of potential further internal organization, including some amount of recombination, nestedness and non-adjacent dependencies. We argue that data-driven, whole-repertoire analyses are fundamental to uncovering the combinatorial complexity of non-human animals and will further facilitate meaningful comparisons with language's combinatoriality.

Fast and accurate short-read alignment with hybrid hash-tree data structure

Rapidly increasing the amount of short-read data generated by NGSs (new-generation sequencers) calls for the development of fast and accurate read alignment programs. The programs based on the hash table (BLAST) and Burrows-Wheeler transform (bwa-mem) are used, and the latter is known to give superior performance. We here present a new algorithm, a hybrid of hash table and suffix tree, which we designed to speed up the alignment of short reads against large reference sequences such as the human genome. The total turnaround time for processing one human genome sample (read depth of 30) is just 31 min with our system while that was more than 25 h with bwa-mem/gatk. The time for the aligner alone is 28 min for our system but around 2 h for bwa-mem. Our new algorithm is 4.4 times faster than bwa-mem while achieving similar accuracy. Variant calling and other downstream analyses after the alignment can be done with open-source tools such as SAMtools and Genome Analysis Toolkit (gatk) packages, as well as our own fast variant caller, which is well parallelized and much faster than gatk.

First detection of the obligate biotroph Phytophthora cyperi causing disease on yellow nutsedge in the United States, and establishment of molecular barcoding sequences for the species

A pathogen causing disease on yellow nutsedge (Cyperus esculentus) growing in and near irrigated areas of onion seed and bulb fields in Idaho and Oregon during July and August, 1996 was morphologically and molecularly characterized. Plant symptoms included necrotic spots, blotches and blighting of leaves, stems (culms) and bracts. Symptomatic tissue contained glistening, white masses of mycelium and oval, semi-papillate sporangia emerging from stomata on sporangiophores. Later, subspherical oogonia with smooth oospores were found embedded in older, infected tissue. Phytophthora cyperi was identified as the causal agent and pathogenicity was confirmed by inoculating healthy nutsedge plants with sporangia from infected plants. Infected samples tested negative using Agdia’s Phytophthora ELISA kit and all efforts to culture the organism on semi-selective or general fungal media failed. To aid future efforts to detect this species, sequences of the two primary barcoding loci, ITS rDNA and mitochondrial cox1 were obtained from the organism and analyzed, finding an unexpectedly large ITS sequence characterized by a ~1300 bp insertion.

Comparative and phylogenetic analysis of the chloroplast genomes of four commonly used medicinal cultivars of Chrysanthemums morifolium

‘Boju’ and ‘Huaiju’ are cultivars of the Chrysanthemum (Chrysanthemum morifolium Ramat.) in the family Asteraceae, valued for their medicinal, tea, and ornamental properties, and valued by individuals. However, the yield and quality of medicinal chrysanthemums are limited by the characteristics of the germplasm resources, including the identification at the varieties and cultivation levels. Currently, research characterizing the chloroplast genomes of medicinal Chrysanthemum flowers is relatively limited. This study conducted chloroplast whole-genome sequencing on two cultivars of Chrysanthemum, ‘Boju’ and ‘Huaiju’, and compared them with the previously published chloroplast genomes of ‘Hangbaiju’ and ‘Gongju’. The study analyzed the chloroplast genome structures of these four medicinal Chrysanthemums, identifying mutation hotspots and clarifying their phylogenetic relationships. The chloroplast genome sizes of four medicinal Chrysanthemum cultivation products ranged from 151,057 to 151,109 bp, with GC content ranging from 37.45% to 37.76%. A total of 134 genes were identified, including 89 protein-coding genes, 37 ribosomal RNA genes, and 8 transfer RNA genes. Comparative genomic analysis revealed 159 large repeat sequences, 276 simple sequence repeats, 1 gene, and 8 intergenic regions identified as highly variable regions. Nucleotide diversity (Pi) values were high (≥ 0.004) for the petN-psbM, trnR-UCU-trnT-GGU, trnT-GGU-psbD, ndhC-trnV-UCA, ycf1, ndhI-ndhG, trnL-UGA-rpl32, rpl32-ndhF, and ndhF-ycf1 fragments, aiding in variety identification. Phylogenetic analysis revealed consistent results between maximum likelihood and Bayesian inference trees, showing that the four medicinal Chrysanthemum cultivars, along with their wild counterparts and related species, evolved as a monophyletic group, forming a sister clade to Artemisia and Ajania. Among the six Chrysanthemum species, the wild Chrysanthemum diverged first (Posterior probability = 1, bootstrap = 1,000), followed by Ajania, while C. indicum and C. morifolium clustered together (Bootstrap = 100), indicating their closest genetic relationship. The chloroplast whole-genome data and characteristic information provided in this study can be used for variety identification, genetic conservation, and phylogenetic analysis within the family Asteraceae.

Efficient Storage and Analysis of Genomic Data: A k-mer Frequency Mapping and Image Representation Method.

k-mer frequencies are crucial for understanding DNA sequence patterns and structure, with applications in motif discovery, genome classification, and short read assembly. However, the exponential increase in the dimension of frequency tables with increasing k-mer length poses storage challenges. In this study, we present a novel method for compressing k-mer data without information loss, aiming to optimize storage and analysis processes. We employed Chaos Game Representation (CGR) to map k-mers to coordinates and used these components to generate raster images of k-mers. The CGR maps were partitioned and labeled based on substrings, with each substring mapped to a subframe, creating a fractal-like structure. The entire k-mer frequency set of each genomic sequence was represented as a single image, with each pixel corresponding to a specific k-mer and its occurrence. This approach reduced file size by up to 16-fold compared to plain text and 3-fold compared to binary format. Furthermore, we demonstrated the feasibility of performing alignment-free similarity analyses on images derived from k-mer frequencies of whole genome sequences from 14 plant species. Our results highlight the potential of this method as a fast and efficient tool for accessing, processing, and analyzing large biological sequence datasets, enabling the retrieval of k-mer frequencies and image reconstruction.

Retraction Note: FFcPsA: a fast finite conventional state using prefix pattern gene search algorithm for large sequence identification

Retraction Note: FFcPsA: a fast finite conventional state using prefix pattern gene search algorithm for large sequence identification

Antibody sequence determinants of viral antigen specificity.

Throughout life, humans experience repeated exposure to viral antigens through infection and vaccination, resulting in the generation of diverse, antigen-specific antibody repertoires. A paramount feature of antibodies that enables their critical contributions in counteracting recurrent and novel pathogens, and consequently fostering their utility as valuable targets for therapeutic and vaccine development, is the exquisite specificity displayed against their target antigens. Yet, there is still limited understanding of the determinants of antibody-antigen specificity, particularly as a function of antibody sequence. In recent years, experimental characterization of antibody repertoires has led to novel insights into fundamental properties of antibody sequences but has been largely decoupled from at-scale antigen specificity analysis. Here, using the LIBRA-seq technology, we generated a large data set mapping antibody sequence to antigen specificity for thousands of B cells, by screening the repertoires of a set of healthy individuals against 20 viral antigens representing diverse pathogens of biomedical significance. Analysis uncovered virus-specific patterns in variable gene usage, gene pairing, somatic hypermutation, as well as the presence of convergent antiviral signatures across multiple individuals, including the presence of public antibody clonotypes. Notably, our results showed that, for B-cell receptors originating from different individuals but leveraging an identical combination of heavy and light chain variable genes, there is a specific CDRH3 identity threshold above which B cells appear to exclusively share the same antigen specificity. This finding provides a quantifiable measure of the relationship between antibody sequence and antigen specificity and further defines experimentally grounded criteria for defining public antibody clonality.IMPORTANCEThe B-cell compartment of the humoral immune system plays a critical role in the generation of antibodies upon new and repeated pathogen exposure. This study provides an unprecedented level of detail on the molecular characteristics of antibody repertoires that are specific to each of the different target pathogens studied here and provides empirical evidence in support of a 70% CDRH3 amino acid identity threshold in pairs of B cells encoded by identical IGHV:IGL(K)V genes, as a means of defining public clonality and therefore predicting B-cell antigen specificity in different individuals. This is of exceptional importance when leveraging public clonality as a method to annotate B-cell receptor data otherwise lacking antigen specificity information. Understanding the fundamental rules of antibody-antigen interactions can lead to transformative new approaches for the development of antibody therapeutics and vaccines against current and emerging viruses.

Harnessing plasticity in sequential metamaterials for ideal shock absorption.

Mechanical metamaterials exhibit interesting properties such as high stiffness at low density1-3, enhanced energy absorption3,4, shape morphing5-7, sequential deformations8-11, auxeticity12-14 and robust waveguiding15,16. Until now, metamaterial design has primarily relied on geometry, and materials nonlinearities such as viscoelasticity, fracture and plasticity have been largely left out of the design rationale. In fact, plastic deformations have been traditionally seen as a failure mode and thereby carefully avoided1,3,17,18. Here we embrace plasticity instead and discover a delicate balance between plasticity and buckling instability, which we term 'yield buckling'. We exploit yield buckling to design metamaterials that buckle sequentially in an arbitrary large sequence of steps whilst keeping a load-bearing capacity. We make use of sequential yield buckling to create metamaterials that combine stiffness and dissipation-two properties that are usually incompatible-and that can be used several times. Hence, our metamaterials exhibit superior shock-absorption performance. Our findings add plasticity to the metamaterial toolbox and make mechanical metamaterials a burgeoning technology with serious potential for mass production.

Transipedia.org: k-mer-based exploration of large RNA sequencing datasets and application to cancer data

Indexing techniques relying on k-mers have proven effective in searching for RNA sequences across thousands of RNA-seq libraries, but without enabling direct RNA quantification. We show here that arbitrary RNA sequences can be quantified in seconds through their decomposition into k-mers, with a precision akin to that of conventional RNA quantification methods. Using an index of the Cancer Cell Line Encyclopedia (CCLE) collection consisting of 1019 RNA-seq samples, we show that k-mer indexing offers a powerful means to reveal non-reference sequences, and variant RNAs induced by specific gene alterations, for instance in splicing factors.

8696 Whole Exome Sequence Analysis in a Naïve Cohort of Congenital Hypopituitarism in a Single Center

Abstract Disclosure: F.Q. Aratani: None. D.P. Di Matteo: None. I.P. de Magalhães: None. P. Frudit: None. L.S. Motomia: None. S.K. Beeby: None. L.R. Barros: None. D.D. Bissegatto: None. L.R. Carvalho: None. Background: Deficiency of one or more pituitary hormones is defined as hypopituitarism. In the literature, molecular diagnosis (MD) is defined in 12% by the Sanger sequencing and large scale sequencing increased this number to 15%. Aim: To perform whole exome sequencing (WES) in a cohort of patients with congenital hypopituitarism (CH) naïve to MD approach. Patients: Nine patients with CH followed in a single Brazilian tertiary center were included. Methods: Libraries were prepared with kits from Agilent and sequenced on Hi-Seq (Illumina). The variants were called following GATK best practices, using the Haplotypecaller and genome version hg38. They were classified in the Franklin by genoox (https://franklin.genoox.com/clinical-db/home). WES that did not pass the platform's initial quality control and variants that did not reach an adequate confidence level (low/medium confidence: VAF < 50%) were excluded. The remaining variants were classified according to ACMG criteria. Results: Three among 9 patients presented allelic variants and aredescribed here. Case 1: A 22-year-old female presented height of 143 cm (-3,13 SDS) at the first visit without signs of puberty, had delayed bone age (DBA), hypoplastic adenohypophysis, interrupted pituitary stalk (IPS) and ectopic neurohypophysis (ENH) at the magnetic resonance imaging (MRI). Hormonal profile showed low E2, GH, FSH and LH. Twoheterozygous missense variants in the ALMS1 gene (c.5450G>A : p.Arg1817GIn; and ALMS1:c.4225G>C: p.Ala1409Pro) were seen in the exome; both classified as VUS according to ACMG criteria. This allelic variant is related to Alstrom Syndrome. Case 2: A 7-year-old female presented with short stature and was diagnosed with GH followed by LH/FSH, TSH and ACTH deficiencies. At MRI presented IPS and ENH. A heterozygous variant in the PROK2 gene c.364C>T p.R122 with a premature stop codon and truncated protein was present and classified as probably pathogenic according to ACMG criteria. This variant was already described with hypogonadotropic hypogonadism (HH) with or without anosmia. Case3: A 15-year-old male was referred with growth hormone deficiency (GHD), DBA, and HH. Growth hormone replacement was started followed by testosterone. Despite delayed puberty, the testes were normal in size. WES showed a variant c.629G>A:p.Trp210*, in hemizygosity in IGSF1 gene and was classified as probably pathogenic according to ACMG criteria. Loss-of-function mutations in IGSF1 may cause an X-linked syndrome of central hypothyroidism, macroorchidism and delayed puberty (delayed rise of testosterone, but normal timing of testicular growth). Conclusion: WES in a cohort of patients with congenital hypopituitarism naïve to molecular diagnosis revealed 33% (3/9) with positive genetic findings, two of them with clinical significance and family segregation according to the genetic inheritance. Presentation: 6/3/2024

Viral genetics and transmission dynamics in the second wave of mpox outbreak in Portugal and forecasting public health scenarios

ABSTRACT In 2023, a second wave of the global mpox epidemic, which is mainly affecting men who have sex with men (MSM), was observed in some countries. Herein, we benefited from a large viral sequence sampling (76/121; 63%) and vast epidemiological data to characterise the re-emergence and circulation of the Monkeypox virus (MPXV) in Portugal during 2023. We also modelled transmission and forecasted public health scenarios through a compartmental susceptible-exposed-infectious-recovered (SEIR) model. Our results suggest that the 2023 mpox wave in Portugal resulted from limited introduction(s) of MPXV belonging to C.1.1 sublineage, hypothetically from Asia, followed by sustained viral transmission and potential exportation to other countries. We estimated that the contribution of the MSM high sexual activity group to mpox transmission was 120 (95% CrI: 30–3553) times higher than that of the low sexual activity group. However, among the high sexual activity group, vaccinated individuals likely contributed approximately eight times less [0.123 (95% CrI: 0.068–0.208)] than the unvaccinated ones. Vaccination was also linked to potential reduced disease severity, with a Mpox Severity Score of 6.0 in the vaccinated group compared to 7.0 in unvaccinated individuals. Scenario analysis indicated that transmission is highly sensitive to sexual behaviour, projecting that a slight increase in the MSM sub-population with high sexual activity can trigger new mpox waves. This study strongly supports that continued vaccination, targeted awareness among risk groups and routine genomic epidemiology is needed to anticipate and respond to novel MPXV threats (e.g. global dissemination of clade I viruses).

Yamadazyma thunbergiae sp. nov., a novel yeast species associated with Bengal clock vines and soil in Okinawa, Japan.

Two strains, designated JCM 36746T and JCM 36749, were isolated from Bengal clock vine (Thunbergia grandiflora) and soil, respectively, in Okinawa, Japan. Analysis of the internal transcribed spacer (ITS) regions and D1/D2 domains of the large subunit rRNA gene sequences revealed identical sequences in both strains, indicating that they belong to the same species. Sequence analysis and physiological characterization identified these strains as representing a novel yeast species in the genus Yamadazyma. The sequence similarities of the concatenated ITS regions and D1/D2 domains indicated that JCM 36746T and JCM 36749 formed a well-supported distinct from closely related species belonging to the Yamadazyma clade, including Candida dendronema, C. diddensiae, C. germanica, C. kanchanaburiensis, C. naeodendra, C. vaughaniae, Y. akitaensis, Y. koratensis, Y. nakazawae, Y. philogaea, Y. phyllophila, Y. siamensis, Y. ubonensis, and three undescribed species, comprising Candida aff. naeodendra/diddensiae Y151, Candida sp. GE19S08, and Yamadazyma sp. strain NYNU 22830. The sequences of the D1/D2 domains and ITS regions differed in nucleotide substitutions by 1.51% and 2.57% or greater, respectively, from those of the previously described and undescribed related species. In addition, the physiological characteristics of the novel species were distinct from those of the closely related described species. On the basis of these findings, we propose the name Yamadazyma thunbergiae sp. nov. to classify this species within the genus Yamadazyma. The holotype used is JCM 36746T (ex-type strains CBS 18614 and NBRC 116657). The MycoBank accession number is MB 853823.

Viral whole genome sequencing reveals high variations in APOBEC3 editing between HPV risk categories.

High-risk human papillomavirus (HPV) infections are responsible for cervical cancer. However, little is known about the differences between HPV types and risk categories regarding their genetic diversity and particularly APOBEC3-induced mutations - which contribute to the innate immune response to HPV. Using a capture-based next-generation sequencing, 156 HPV whole genome sequences covering 43 HPV types were generated from paired cervical and anal swabs of 30 Togolese female sex workers (FSWs) sampled in 2017. Genetic diversity and APOBEC3-induced mutations were assessed at the viral whole genome and gene levels. Thirty-four pairwise sequence comparisons covering 24 HPV types in cervical and anal swabs revealed identical infections in the two anatomical sites. Differences in genetic diversity among HPV types was observed between patients. The E6 gene was significantly less conserved in low-risk HPVs (lrHPVs) compared to high-risk HPVs (hrHPVs) (p = 0.009). APOBEC3-induced mutations were found to be more common in lrHPVs than in hrHPVs (p = 0.005), supported by our data and by using large HPV sequence collections from the GenBank database. Focusing on the most common lrHPVs 6 and 11 and hrHPVs 16 and 18, APOBEC3-induced mutations were predominantly found in the E4 and E6 genes in lrHPVs, but were almost absent in these genes in hrHPVs. The variable APOBEC3 mutational signatures could contribute to the different oncogenic potentials between HPVs. Further studies are needed to conclusively determine whether APOBEC3 editing levels are associated to the carcinogenic potential of HPVs at the type and sublineage scales.

Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining

We describe a process for rapid antibody affinity optimization by repertoire mining to identify clones across B cell clonal lineages based on convergent immune responses where antigen-specific clones with the same heavy (VH) and light chain germline segment pairs, or parallel lineages, bind a single epitope on the antigen. We use this convergence framework to mine unique and distinct VH lineages from rat anti-triggering receptor on myeloid cells 2 (TREM2) antibody repertoire datasets with high diversity in the third complementarity-determining loop region (CDR H3) to further affinity-optimize a high-affinity agonistic anti-TREM2 antibody while retaining critical functional properties. Structural analyses confirm a nearly identical binding mode of anti-TREM2 variants with subtle but significant structural differences in the binding interface. Parallel lineage repertoire mining is uniquely tailored to rationally explore the large CDR H3 sequence space in antibody repertoires and can be easily and generally applied to antibodies discovered in vivo.

Discovery of a novel Wolbachia in Heterodera expands nematode host distribution.

Bioinformatics sequence data mining can reveal hidden microbial symbionts that might normally be filtered and removed as contaminants. Data mining can be helpful to detect Wolbachia, a widespread bacterial endosymbiont in insects and filarial nematodes whose distribution in plant-parasitic nematodes (PPNs) remains underexplored. To date, Wolbachia has only been reported a few PPNs, yet nematode-infecting Wolbachia may have been widespread in the evolutionary history of the phylum based on evidence of horizontal gene transfers, suggesting there may be undiscovered Wolbachia infections in PPNs. The goal of this study was to more broadly sample PPN Wolbachia strains in tylenchid nematodes to enable further comparative genomic analyses that may reveal Wolbachia's role and identify targets for biocontrol. Published whole-genome shotgun assemblies and their raw sequence data from 33 Meloidogyne spp. assemblies, seven Globodera spp. assemblies, and seven Heterodera spp. assemblies were analyzed to look for Wolbachia. No Wolbachia was found in Meloidogyne spp. and Globodera spp., but among seven genome assemblies for Heterodera spp., an H. schachtii assembly from the Netherlands was found to have a large Wolbachia-like sequence that, when re-assembled from reads, formed a complete, circular genome. Detailed analyses comparing read coverage, GC content, pseudogenes, and phylogenomic patterns clearly demonstrated that the H. schachtii Wolbachia represented a novel strain (hereafter, denoted wHet). Phylogenomic tree construction with PhyloBayes showed wHet was most closely related to another PPN Wolbachia, wTex, while 16S rRNA gene analysis showed it clustered with other Heterodera Wolbachia assembled from sequence databases. Pseudogenes in wHet suggested relatedness to the PPN clade, as did the lack of significantly enriched GO terms compared to PPN Wolbachia strains. It remains unclear whether the lack of Wolbachia in other published H. schachtii isolates represents the true absence of the endosymbiont from some hosts.

DETR-ORD: An Improved DETR Detector for Oriented Remote Sensing Object Detection with Feature Reconstruction and Dynamic Query

Optical remote sensing images often feature high resolution, dense target distribution, and uneven target sizes, while transformer-based detectors like DETR reduce manually designed components, DETR does not support arbitrary-oriented object detection and suffers from high computational costs and slow convergence when handling large sequences of images. Additionally, bipartite graph matching and the limit on the number of queries result in transformer-based detectors performing poorly in scenarios with multiple objects and small object sizes. We propose an improved DETR detector for Oriented remote sensing object detection with Feature Reconstruction and Dynamic Query, termed DETR-ORD. It introduces rotation into the transformer architecture for oriented object detection, reduces computational cost with a hybrid encoder, and includes an IFR (image feature reconstruction) module to address the loss of positional information due to the flattening operation. It also uses ATSS to select auxiliary dynamic training queries for the decoder. This improved DETR-based detector enhances detection performance in challenging oriented optical remote sensing scenarios with similar backbone network parameters. Our approach achieves superior results on most optical remote sensing datasets, such as DOTA-v1.5 (72.07% mAP) and DIOR-R (66.60% mAP), surpassing the baseline detector.

Fault imaging using earthquake sequences: a revised seismotectonic model for the Albstadt Shear Zone, Southwest Germany

In Germany, the highest seismic hazard is associated with the Albstadt Shear Zone (ASZ) in the western Swabian Jura, a low mountain range in southwest Germany. The region is affected by continuous micro-seismic activity with the potential for damaging earthquakes (nine events with ML≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge $$\\end{document} 5 in the 20th\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{th}$$\\end{document} century). Within the AlpArray and StressTransfer projects nine temporary seismic stations have been installed in the region of the ASZ to densify the permanent seismic monitoring. In October 2018 and September 2019, the state seismological survey (LED) detected two low-magnitude earthquake sequences with hundreds of events in the area. The temporarily densified local network allows us to systematically analyze these sequences and to search for other sequences by applying a template-matching routine on data from 2018 to 2020. In total, six earthquake sequences could be identified with at least 10 events. The four largest sequences (> 50 events) consist of two fore- and aftershock sequence and two earthquake swarms. Earthquake swarms were so far not observed around the ASZ. Precise relative hypocenter relocations and the determination of fault-plane solutions allow us to propose a seismotectonic model based on the three imaged fault types: (a) The well-known NNE-SSW striking sinistral strike-slip ASZ at depths of 5-10 km, (b) a NW-SE striking dextral strike-slip fault zone at depths of 11-15 km beneath the Hohenzollerngraben (HZG), a shallow, apparently aseismic NW-SE striking graben structure; this NW-SE fault zone possibly is an inherited zone of weakness in the basement and facilitated the development of the HZG and (c) at the intersection of the ASZ with the NW-SE fault zone, complex faulting in form of NNW-SSE striking sinistral strike-slip and normal faulting possibly to accommodate local stresses.

The opposite aging effect to single cell transcriptome profile among cell subsets.

Comparing transcriptome profiling between younger and older samples reveals genes related to aging and provides insight into the biological functions affected by aging. Recent research has identified sex, tissue, and cell type-specific age-related changes in gene expression. This study reports the overall picture of the opposite aging effect, in which aging increases gene expression in one cell subset and decreases it in another cell subset. Using the Tabula Muris Senis dataset, a large public single-cell RNA sequencing dataset from mice, we compared the effects of aging in different cell subsets. As a result, the opposite aging effect was observed widely in the genes, particularly enriched in genes related to ribosomal function and translation. The opposite aging effect was observed in the known aging-related genes. Furthermore, the opposite aging effect was observed in the transcriptome diversity quantified by the number of expressed genes and the Shannon entropy. This study highlights the importance of considering the cell subset when intervening with aging-related genes.

Metapipeline-DNA: A Comprehensive Germline & Somatic Genomics Nextflow Pipeline.

DNA sequencing is becoming more affordable and faster through advances in high-throughput technologies. This rise in data availability has contributed to the development of novel algorithms to elucidate previously obscure features and led to an increased reliance on complex workflows to integrate such tools into analyses pipelines. To facilitate the analysis of DNA sequencing data, we created metapipeline-DNA, a highly configurable and extensible pipeline. It encompasses a broad range of processing including raw sequencing read alignment and recalibration, variant calling, quality control and subclonal reconstruction. Metapipeline-DNA also contains configuration options to select and tune analyses while being robust to failures. This standardizes and simplifies the ability to analyze large DNA sequencing in both clinical and research settings. Metapipeline-DNA is an open-source Nextflow pipeline under the GPLv2 license and is freely available at https://github.com/uclahs-cds/metapipeline-DNA.