Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing [RESEARCH]
Fascioscapulohumeral muscular dystrophy (FSHD) is caused by a unique genetic mechanism that relies on contraction and hypomethylation of the D4Z4 macrosatellite array on the Chromosome 4q telomere allowing ectopic expression of the DUX4 gene in skeletal muscle. Genetic analysis is difficult because of the large size and repetitive nature of the array, a nearly identical array on the 10q telomere, and the presence of divergent D4Z4 arrays scattered throughout the genome. Here, we combine nanopore long-read sequencing with Cas9-targeted enrichment of 4q and 10q D4Z4 arrays for comprehensive genetic analysis including determi...
Source: Genome Research - October 13, 2023 Category: Genetics & Stem Cells Authors: Butterfield, R. J., Dunn, D. M., Duval, B., Moldt, S., Weiss, R. B. Tags: RESEARCH Source Type: research
ESICCC as a systematic computational framework for evaluation, selection, and integration of cell-cell communication inference methods [METHOD]
Cell-cell communication (CCC) is critical for determining cell fates and functions in multicellular organisms. With the advent of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST), an increasing number of CCC inference methods have been developed. Nevertheless, a thorough comparison of their performance is yet to be conducted. To fill the gap, we developed a systematic benchmark framework called ESICCC to evaluate 18 ligand-receptor (LR) inference methods and 5 ligand/receptor-targets inference methods using a total of 116 datasets, including 15 ST datasets, 15 sets of cell line perturbation data, two...
Source: Genome Research - October 12, 2023 Category: Genetics & Stem Cells Authors: Luo, J., Deng, M., Zhang, X., Sun, X. Tags: METHOD Source Type: research
Accurate and fast graph-based pangenome annotation and clustering with ggCaller [METHOD]
Bacterial genomes differ in both gene content and sequence mutations, which underlie extensive phenotypic diversity, including variation in susceptibility to antimicrobials or vaccine-induced immunity. To identify and quantify important variants, all genes within a population must be predicted, functionally annotated, and clustered, representing the "pangenome." Despite the volume of genome data available, gene prediction and annotation are currently conducted in isolation on individual genomes, which is computationally inefficient and frequently inconsistent across genomes. Here, we introduce the open-source software grap...
Source: Genome Research - October 6, 2023 Category: Genetics & Stem Cells Authors: Horsfield, S. T., Tonkin-Hill, G., Croucher, N. J., Lees, J. A. Tags: METHOD Source Type: research
An 11-point time course midgut transcriptome across 72 h after bloodfeeding provides detailed temporal resolution of transcript expression in the arbovirus vector, Aedes aegypti [RESOURCES]
This study provides a powerful resource for the analysis of genomic features that coordinate the rapid and complex transcriptional program induced by mosquito bloodfeeding. (Source: Genome Research)
Source: Genome Research - October 6, 2023 Category: Genetics & Stem Cells Authors: Tsujimoto, H., Adelman, Z. N. Tags: RESOURCES Source Type: research
Dissecting and improving gene regulatory network inference using single-cell transcriptome data [METHOD]
Single-cell transcriptome data has been widely used to reconstruct gene regulatory networks (GRNs) controlling critical biological processes such as development and differentiation. Although a growing list of algorithms has been developed to infer GRNs using such data, achieving an inference accuracy consistently higher than random guessing has remained challenging. To address this, it is essential to delineate how the accuracy of regulatory inference is limited. Here, we systematically characterized factors limiting the accuracy of inferred GRNs and demonstrated that using pre-mRNA information can help improve regulatory ...
Source: Genome Research - October 5, 2023 Category: Genetics & Stem Cells Authors: Xue, L., Wu, Y., Lin, Y. Tags: METHOD Source Type: research
Fast and accurate out-of-core PCA framework for large scale biobank data [METHOD]
Principal component analysis (PCA) is widely used in statistics, machine learning, and genomics for dimensionality reduction and uncovering low-dimensional latent structure. To address the challenges posed by ever-growing data size, fast and memory-efficient PCA methods have gained prominence. In this paper, we propose a novel randomized singular value decomposition (RSVD) algorithm implemented in PCAone, featuring a window-based optimization scheme that enables accelerated convergence while improving the accuracy. Additionally, PCAone incorporates out-of-core and multithreaded implementations for the existing Implicitly R...
Source: Genome Research - October 5, 2023 Category: Genetics & Stem Cells Authors: Li, Z., Meisner, J., Albrechtsen, A. Tags: METHOD Source Type: research
Comprehensive isoform-level analysis reveals the contribution of alternative isoforms to venom evolution and repertoire diversity [RESEARCH]
In this study, we present a full-length isoform-level profiling workflow integrating multiple RNA sequencing technologies, allowing us to reconstruct a high-resolution transcriptome landscape of venom genes in the parasitoid wasp Pteromalus puparum. Our findings demonstrate that more than half of the venom genes generate multiple isoforms within the venom gland. Through mass spectrometry analysis, we confirm that alternative splicing contributes to the diversity of venom proteins, acting as a mechanism for expanding the venom repertoire. Notably, we identified seven venom genes that exhibit distinct isoform usages between ...
Source: Genome Research - October 5, 2023 Category: Genetics & Stem Cells Authors: Ye, X., He, C., Yang, Y., Sun, Y. H., Xiong, S., Chan, K. C., Si, Y., Xiao, S., Zhao, X., Lin, H., Mei, Y., Yao, Y., Ye, G., Wu, F., Fang, Q. Tags: RESEARCH Source Type: research
Phylogenetic modeling of enhancer shifts in African mole-rats reveals regulatory changes associated with tissue-specific traits [RESEARCH]
Changes in gene regulation are thought to underlie most phenotypic differences between species. For subterranean rodents such as the naked mole-rat, proposed phenotypic adaptations include hypoxia tolerance, metabolic changes, and cancer resistance. However, it is largely unknown what regulatory changes may associate with these phenotypic traits, and whether these are unique to the naked mole-rat, the mole-rat clade, or are also present in other mammals. Here, we investigate regulatory evolution in the heart and liver from two African mole-rat species and two rodent outgroups using genome-wide epigenomic profiling. First, ...
Source: Genome Research - October 5, 2023 Category: Genetics & Stem Cells Authors: Parey, E., Fernandez-Aroca, D., Frost, S., Uribarren, A., Park, T. J., Zöttl, M., Smith, E. S. J., Berthelot, C., Villar, D. Tags: RESEARCH Source Type: research
Deciphering D4Z4 CpG methylation gradients in fascioscapulohumeral muscular dystrophy using nanopore sequencing [RESEARCH]
Fascioscapulohumeral muscular dystrophy (FSHD) is caused by a unique genetic mechanism that relies on contraction and hypomethylation of the D4Z4 macrosatellite array on the Chromosome 4q telomere allowing ectopic expression of the DUX4 gene in skeletal muscle. Genetic analysis is difficult because of the large size and repetitive nature of the array, a nearly identical array on the 10q telomere, and the presence of divergent D4Z4 arrays scattered throughout the genome. Here, we combine nanopore long-read sequencing with Cas9-targeted enrichment of 4q and 10q D4Z4 arrays for comprehensive genetic analysis including determi...
Source: Genome Research - October 5, 2023 Category: Genetics & Stem Cells Authors: Butterfield, R. J., Dunn, D. M., Duval, B., Moldt, S., Weiss, R. B. Tags: RESEARCH Source Type: research
Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development [RESEARCH]
Mice harbor ~2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss...
Source: Genome Research - October 5, 2023 Category: Genetics & Stem Cells Authors: Gerdes, P., Chan, D., Lundberg, M., Sanchez-Luque, F. J., Bodea, G. O., Ewing, A. D., Faulkner, G. J., Richardson, S. R. Tags: RESEARCH Source Type: research
Elasmobranch genome sequencing reveals evolutionary trends of vertebrate karyotype organization [RESEARCH]
Genomic studies of vertebrate chromosome evolution have long been hindered by the scarcity of chromosome-scale DNA sequences of some key taxa. One of those limiting taxa has been the elasmobranchs (sharks and rays), which harbor species often with numerous chromosomes and enlarged genomes. Here, we report the chromosome-scale genome assembly for the zebra shark Stegostoma tigrinum, an endangered species that has a relatively small genome among sharks (3.71 Gb), as well as for the whale shark Rhincodon typus. Our analysis using a male–female comparison identified an X Chromosome, the first genomically characterized sh...
Source: Genome Research - October 4, 2023 Category: Genetics & Stem Cells Authors: Yamaguchi, K., Uno, Y., Kadota, M., Nishimura, O., Nozu, R., Murakumo, K., Matsumoto, R., Sato, K., Kuraku, S. Tags: RESEARCH Source Type: research
Transposons contribute to the functional diversification of the head, gut, and ovary transcriptomes across Drosophila natural strains [RESEARCH]
Transcriptomes are dynamic, with cells, tissues, and body parts expressing particular sets of transcripts. Transposable elements (TEs) are a known source of transcriptome diversity; however, studies often focus on a particular type of chimeric transcript, analyze single body parts or cell types, or are based on incomplete TE annotations from a single reference genome. In this work, we have implemented a method based on de novo transcriptome assembly that minimizes the potential sources of errors while identifying a comprehensive set of gene-TE chimeras. We applied this method to the head, gut, and ovary dissected from five...
Source: Genome Research - October 4, 2023 Category: Genetics & Stem Cells Authors: Coronado-Zamora, M., Gonzalez, J. Tags: RESEARCH Source Type: research
The rate of de novo structural variation is increased in in vitro-produced offspring and preferentially affects the paternal genome [RESEARCH]
Assisted reproductive technologies (ARTs), including in vitro maturation and fertilization (IVF), are increasingly used in human and animal reproduction. Whether these technologies directly affect the rate of de novo mutation (DNM), and to what extent, has been a matter of debate. Here we take advantage of domestic cattle, characterized by complex pedigrees that are ideally suited to detect DNMs and by the systematic use of ART, to study the rate of de novo structural variation (dnSV) in this species and how it is impacted by IVF. By exploiting features of associated de novo point mutations (dnPMs) and dnSVs in clustered D...
Source: Genome Research - October 4, 2023 Category: Genetics & Stem Cells Authors: Lee, Y.-L., Bouwman, A. C., Harland, C., Bosse, M., Costa Monteiro Moreira, G., Veerkamp, R. F., Mullaart, E., Cambisano, N., Groenen, M. A. M., Karim, L., Coppieters, W., Georges, M., Charlier, C. Tags: RESEARCH Source Type: research
Telomerase-independent survival leads to a mosaic of complex subtelomere rearrangements in Chlamydomonas reinhardtii [RESEARCH]
Telomeres and subtelomeres, the genomic regions located at chromosome extremities, are essential for genome stability in eukaryotes. In the absence of the canonical maintenance mechanism provided by telomerase, telomere shortening induces genome instability. The landscape of the ensuing genome rearrangements is not accessible by short-read sequencing. Here, we leverage Oxford Nanopore Technologies long-read sequencing to survey the extensive repertoire of genome rearrangements in telomerase mutants of the model green microalga Chlamydomonas reinhardtii. In telomerase-mutant strains grown for hundreds of generations, most c...
Source: Genome Research - October 4, 2023 Category: Genetics & Stem Cells Authors: Chaux, F., Agier, N., Garrido, C., Fischer, G., Eberhard, S., Xu, Z. Tags: RESEARCH Source Type: research
Genetic inhibitors of APOBEC3B-induced mutagenesis [RESEARCH]
The cytidine deaminases APOBEC3A (A3A) and APOBEC3B (A3B) are prominent mutators of human cancer genomes. However, tumor-specific genetic modulators of APOBEC-induced mutagenesis are poorly defined. Here, we used a screen to identify 61 gene deletions that increase A3B-induced mutations in yeast. We also determined whether each deletion was epistatic with Ung1 loss, which indicated whether the encoded factors participate in the homologous recombination (HR)–dependent bypass of A3B/Ung1-dependent abasic sites or suppress A3B-catalyzed deamination by protecting against aberrant formation of single-stranded DNA (ssDNA)....
Source: Genome Research - October 3, 2023 Category: Genetics & Stem Cells Authors: Mertz, T. M., Rice-Reynolds, E., Nguyen, L., Wood, A., Cordero, C., Bray, N., Harcy, V., Vyas, R. K., Mitchell, D., Lobachev, K., Roberts, S. A. Tags: RESEARCH Source Type: research
