Localizing unmapped sequences with families to validate the Telomere-to-Telomere assembly and identify new hotspots for genetic diversity [METHOD]
Although it is ubiquitous in genomics, the current human reference genome (GRCh38) is incomplete: It is missing large sections of heterochromatic sequence, and as a singular, linear reference genome, it does not represent the full spectrum of human genetic diversity. To characterize gaps in GRCh38 and human genetic diversity, we developed an algorithm for sequence location approximation using nuclear families (ASLAN) to identify the region of origin of reads that do not align to GRCh38. Using unmapped reads and variant calls from whole-genome sequences (WGSs), ASLAN uses a maximum likelihood model to identify the most like...
Source: Genome Research - October 25, 2023 Category: Genetics & Stem Cells Authors: Chrisman, B., He, C., Jung, J.-Y., Stockham, N., Paskov, K., Washington, P., Petereit, J., Wall, D. P. Tags: METHOD Source Type: research
Analyses of 600+ insect genomes reveal repetitive element dynamics and highlight biodiversity-scale repeat annotation challenges [RESEARCH]
Repetitive elements (REs) are integral to the composition, structure, and function of eukaryotic genomes, yet remain understudied in most taxonomic groups. We investigated REs across 601 insect species and report wide variation in RE dynamics across groups. Analysis of associations between REs and protein-coding genes revealed dynamic evolution at the interface between REs and coding regions across insects, including notably elevated RE–gene associations in lineages with abundant long interspersed nuclear elements (LINEs). We leveraged this large, empirical data set to quantify impacts of long-read technology on RE d...
Source: Genome Research - October 25, 2023 Category: Genetics & Stem Cells Authors: Sproul, J. S., Hotaling, S., Heckenhauer, J., Powell, A., Marshall, D., Larracuente, A. M., Kelley, J. L., Pauls, S. U., Frandsen, P. B. Tags: RESEARCH Source Type: research
Nucleosome repositioning in chronic lymphocytic leukemia [RESEARCH]
The location of nucleosomes in the human genome determines the primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy and its implications in primary cancer cells is scarce. Here, we conducted a genome-wide comparison of high-resolution nucleosome maps in peripheral blood B cells from patients with chronic lymphocytic leukemia (CLL) and healthy individuals at single-base-pair resolution. Our investigation uncovered significant changes of nucleosome positioning in CLL. Globally, the spacing between nucleosomes—the nucleosome repeat l...
Source: Genome Research - October 24, 2023 Category: Genetics & Stem Cells Authors: Piroeva, K. V., McDonald, C., Xanthopoulos, C., Fox, C., Clarkson, C. T., Mallm, J.-P., Vainshtein, Y., Ruje, L., Klett, L. C., Stilgenbauer, S., Mertens, D., Kostareli, E., Rippe, K., Teif, V. B. Tags: RESEARCH Source Type: research
Genome-wide chromatin interaction profiling reveals vital role of super-enhancers and rearrangements in host enhancer contacts during BmNPV infection [RESEARCH]
As influential regulatory elements in the genome, enhancers control gene expression under specific cellular conditions, and such connections are dynamic under different conditions. However, due to the lack of genome-wide enhancer-gene connection map, the roles and regulatory pattern of enhancers were poorly investigated in insects, and the dynamic changes of enhancer contacts and functions under different conditions remain elusive. Here, combining Hi-C, ATAC-seq and H3K27ac ChIP-seq data, we generated the genome-wide enhancer-gene map of silkworm, and identified super-enhancers with the role in regulating the expression of...
Source: Genome Research - October 23, 2023 Category: Genetics & Stem Cells Authors: Zhao, S., Li, Y., Chen, G., Wang, X., Chen, N., Wu, X. Tags: RESEARCH Source Type: research
Transposon accumulation at xenobiotic gene family loci in aphids [RESEARCH]
The evolution of resistance is a major challenge for the sustainable control of pests and pathogens. Thus, a deeper understanding of the evolutionary and genomic mechanisms underpinning resistance evolution is required to safeguard health and food production. Several studies have implicated transposable elements (TEs) in xenobiotic-resistance evolution in insects. However, analyses are generally restricted to one insect species and/or one or a few xenobiotic gene families (XGFs). We examine evidence for TE accumulation at XGFs by performing a comparative genomic analysis across 20 aphid genomes, considering major subsets o...
Source: Genome Research - October 18, 2023 Category: Genetics & Stem Cells Authors: Baril, T., Pym, A., Bass, C., Hayward, A. Tags: RESEARCH Source Type: research
Characterization of human transcription factor function and patterns of gene regulation in HepG2 cells [RESEARCH]
Transcription factors (TFs) are trans-acting proteins that bind cis-regulatory elements (CREs) in DNA to control gene expression. Here, we analyzed the genomic localization profiles of 529 sequence-specific TFs and 151 cofactors and chromatin regulators in the human cancer cell line HepG2, for a total of 680 broadly-termed DNA-Associated Proteins (DAPs). We used this deep collection to model each TF's impact on gene expression, and identified a cohort of 26 candidate transcriptional repressors. We examine High Occupancy Target (HOT) sites in the context of three-dimensional genome organization and show biased motif placeme...
Source: Genome Research - October 18, 2023 Category: Genetics & Stem Cells Authors: Moyers, B. A., Partridge, E. C., Mackiewicz, M., Betti, M. J., Darji, R., Meadows, S. K., Newberry, K. M., Brandsmeier, L. A., Wold, B. J., Mendenhall, E. M., Myers, R. M. Tags: RESEARCH 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 13, 2023 Category: Genetics & Stem Cells Authors: Tsujimoto, H., Adelman, Z. N. Tags: RESOURCES Source Type: research
Accurate and fast graph-based pangenome annotation and clustering with ggCaller [METHODS]
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 13, 2023 Category: Genetics & Stem Cells Authors: Horsfield, S. T., Tonkin-Hill, G., Croucher, N. J., Lees, J. A. Tags: METHODS Source Type: research
Dissecting and improving gene regulatory network inference using single-cell transcriptome data [METHODS]
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 13, 2023 Category: Genetics & Stem Cells Authors: Xue, L., Wu, Y., Lin, Y. Tags: METHODS Source Type: research
Fast and accurate out-of-core PCA framework for large scale biobank data [METHODS]
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 13, 2023 Category: Genetics & Stem Cells Authors: Li, Z., Meisner, J., Albrechtsen, A. Tags: METHODS 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 13, 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 13, 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
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 13, 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
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 fro...
Source: Genome Research - October 13, 2023 Category: Genetics & Stem Cells Authors: Coronado-Zamora, M., Gonzalez, J. 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 13, 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
