The pig pangenome provides insights into the roles of coding structural variations in genetic diversity and adaptation [RESOURCES]
Structural variations have emerged as an important driving force for genome evolution and phenotypic variation in various organisms, yet their contributions to genetic diversity and adaptation in domesticated animals remain largely unknown. Here we constructed a pangenome based on 250 sequenced individuals from 32 pig breeds in Eurasia and systematically characterized coding sequence presence/absence variations (PAVs) within pigs. We identified 308.3-Mb nonreference sequences and 3438 novel genes absent from the current reference genome. Gene PAV analysis showed that 16.8% of the genes in the pangene catalog undergo PAV. A...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Li, Z., Liu, X., Wang, C., Li, Z., Jiang, B., Zhang, R., Tong, L., Qu, Y., He, S., Chen, H., Mao, Y., Li, Q., Pook, T., Wu, Y., Zan, Y., Zhang, H., Li, L., Wen, K., Chen, Y. Tags: RESOURCES Source Type: research
Single-nucleus transcriptomic mapping uncovers targets for traumatic brain injury [RESOURCES]
In this study, we mapped the transcriptome atlas of murine SVZ and its responses to mTBI at the single-cell level. We observed cell-specific gene expression changes following mTBI and unveiled diverse cell-to-cell interaction networks that influence a wide array of cellular processes. Moreover, we report novel neurogenesis lineage trajectories and related key transcription factors, which we validate through loss-of-function experiments. Specifically, we validate the role of Tcf7l1, a cell cycle gene regulator, in promoting neural stem cell differentiation toward the neuronal lineage after mTBI, providing a potential target...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Yang, Q., Zhang, L., Li, M., Xu, Y., Chen, X., Yuan, R., Ou, X., He, M., Liao, M., Zhang, L., Dai, H., Lv, M., Xie, X., Liang, W., Chen, X. Tags: RESOURCES Source Type: research
Multiscale network modeling reveals the gene regulatory landscape driving cancer prognosis in 32 cancer types [RESOURCES]
In this study, we performed a systematic analysis of coexpression networks in 32 cancer types. Our analysis identified 4749 prognostic modules that play a vital role in regulating cancer progression. Integrative epigenomic analyses revealed that these modules were regulated by interactions between gene expression and methylation. Coregulated genes of network modules were enriched in chromosome cytobands and preferentially localized in open chromatin regions. The preserved network modules formed 330 module clusters that resided in chromosome hot spots. The cancer-type-specific prognostic modules participated in unique essen...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Xu, P., Zhang, B. Tags: RESOURCES Source Type: research
ESICCC as a systematic computational framework for evaluation, selection, and integration of cell-cell communication inference methods [METHODS]
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 performances is yet to be conducted. To fill this gap, we developed a systematic benchmark framework called ESICCC to evaluate 18 ligand-receptor (LR) inference methods and five ligand/receptor-target inference methods using a total of 116 data sets, including 15 ST data sets, 15 sets of cell line perturbation dat...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Luo, J., Deng, M., Zhang, X., Sun, X. Tags: METHODS Source Type: research
Infernape uncovers cell type-specific and spatially resolved alternative polyadenylation in the brain [METHODS]
This study presents Infernape to identify PAs from scRNA-seq and spatial data, and highlights the role of alternative PAs in neuronal gene regulation. (Source: Genome Research)
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Kang, B., Yang, Y., Hu, K., Ruan, X., Liu, Y.-L., Lee, P., Lee, J., Wang, J., Zhang, X. Tags: METHODS Source Type: research
Latent feature extraction with a prior-based self-attention framework for spatial transcriptomics [METHODS]
Rapid advances in spatial transcriptomics (ST) have revolutionized the interrogation of spatial heterogeneity and increase the demand for comprehensive methods to effectively characterize spatial domains. As a prerequisite for ST data analysis, spatial domain characterization is a crucial step for downstream analyses and biological implications. Here we propose a prior-based self-attention framework for spatial transcriptomics (PAST), a variational graph convolutional autoencoder for ST, which effectively integrates prior information via a Bayesian neural network, captures spatial patterns via a self-attention mechanism, a...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Li, Z., Chen, X., Zhang, X., Jiang, R., Chen, S. Tags: METHODS Source Type: research
Identifying crossovers and shared genetic material in whole genome sequencing data from families [METHODS]
Large, whole-genome sequencing (WGS) data sets containing families provide an important opportunity to identify crossovers and shared genetic material in siblings. However, the high variant calling error rates of WGS in some areas of the genome can result in spurious crossover calls, and the special inheritance status of the X Chromosome presents challenges. We have developed a hidden Markov model that addresses these issues by modeling the inheritance of variants in families in the presence of error-prone regions and inherited deletions. We call our method PhasingFamilies. We validate PhasingFamilies using the platinum ge...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Paskov, K., Chrisman, B., Stockham, N., Washington, P. Y., Dunlap, K., Jung, J.-Y., Wall, D. P. Tags: METHODS Source Type: research
Localizing unmapped sequences with families to validate the Telomere-to-Telomere assembly and identify new hotspots for genetic diversity [METHODS]
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 - November 8, 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: METHODS 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 - November 8, 2023 Category: Genetics & Stem Cells Authors: Baril, T., Pym, A., Bass, C., Hayward, A. Tags: RESEARCH 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 - November 8, 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
Single-cell transcriptome and metagenome profiling reveals the genetic basis of rumen functions and convergent developmental patterns in ruminants [RESEARCH]
The rumen undergoes developmental changes during maturation. To characterize this understudied dynamic process, we profiled single-cell transcriptomes of about 308,000 cells from the rumen tissues of sheep and goats at 17 time points. We built comprehensive transcriptome and metagenome atlases from early embryonic to rumination stages, and recapitulated histomorphometric and transcriptional features of the rumen, revealing key transitional signatures associated with the development of ruminal cells, microbiota, and core transcriptional regulatory networks. In addition, we identified and validated potential cross-talk betwe...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Deng, J., Liu, Y.-J., Wei, W.-T., Huang, Q.-X., Zhao, L.-P., Luo, L.-Y., Zhu, Q., Zhang, L., Chen, Y., Ren, Y.-L., Jia, S.-G., Lin, Y.-L., Yang, J., Lv, F.-H., Zhang, H.-P., Li, F.-E., Li, L., Li, M.-H. Tags: RESEARCH Source Type: research
GC-biased gene conversion drives accelerated evolution of ultraconserved elements in mammalian and avian genomes [RESEARCH]
Ultraconserved elements (UCEs) are the most conserved regions among the genomes of evolutionarily distant species and are thought to play critical biological functions. However, some UCEs rapidly evolved in specific lineages, and whether they contributed to adaptive evolution is still controversial. Here, using an increased number of sequenced genomes with high taxonomic coverage, we identified 2191 mammalian UCEs and 5938 avian UCEs from 95 mammal and 94 bird genomes, respectively. Our results show that these UCEs are functionally constrained and that their adjacent genes are prone to widespread expression with low expres...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Liu, A., Wang, N., Xie, G., Li, Y., Yan, X., Li, X., Zhu, Z., Li, Z., Yang, J., Meng, F., Dou, M., Chen, W., Ma, N., Jiang, Y., Gao, Y., Wang, Y. Tags: RESEARCH Source Type: research
Clustered and diverse transcription factor binding underlies cell type specificity of enhancers for housekeeping genes [RESEARCH]
Housekeeping genes are considered to be regulated by common enhancers across different tissues. Here we report that most of the commonly expressed mouse or human genes across different cell types, including more than half of the previously identified housekeeping genes, are associated with cell type–specific enhancers. Furthermore, the binding of most transcription factors (TFs) is cell type–specific. We reason that these cell type specificities are causally related to the collective TF recruitment at regulatory sites, as TFs tend to bind to regions associated with many other TFs and each cell type has a unique...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Zhu, I., Landsman, D. 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 - November 8, 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
A DNA methylation haplotype block landscape in human tissues and preimplantation embryos reveals regulatory elements defined by comethylation patterns [RESEARCH]
DNA methylation and associated regulatory elements play a crucial role in gene expression regulation. Previous studies have focused primarily on the distribution of mean methylation levels. Advances in whole-genome bisulfite sequencing (WGBS) have enabled the characterization of DNA methylation haplotypes (MHAPs), representing CpG sites from the same read fragment on a single chromosome, and the subsequent identification of methylation haplotype blocks (MHBs), in which adjacent CpGs on the same fragment are comethylated. Using our expert-curated WGBS datasets, we report comprehensive landscapes of MHBs in 17 representative...
Source: Genome Research - November 8, 2023 Category: Genetics & Stem Cells Authors: Feng, Y., Zhang, Z., Hong, Y., Ding, Y., Liu, L., Gao, S., Fang, H., Shi, J. Tags: RESEARCH Source Type: research
