Featured
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| Open AccessSystematic detection of co-infection and intra-host recombination in more than 2 million global SARS-CoV-2 samples
SARS-CoV-2 coinfections may lead to recombination events which could be important in the emergence of new variants. Here, the authors develop an automated bioinformatics pipeline to identify coinfections in genomic data and test it on >2 million publicly available raw read data sets collected globally.
- Orsolya Anna Pipek
- , Anna Medgyes-Horváth
- & István Csabai
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Article
| Open AccessDiffDomain enables identification of structurally reorganized topologically associating domains
Topologically associating domains (TADs) are critical structural units in 3D genome organization, and their reorganization between health and disease states is associated with essential genome functions. However, computational methods for identifying reorganized TADs are still in the early stages of development. Here, the authors present an algorithm leveraging random matrix theory to identify reorganized TADs.
- Dunming Hua
- , Ming Gu
- & Dechao Tian
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Article
| Open AccessIntegrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas
Frugivory evolved multiple times in mammals, including bats. Here, the authors use integrative single-cell sequencing on fruit and insect bat kidneys and pancreases and identify cell population, gene expression and regulatory differences associated with frugivory that also relate to diabetes.
- Wei E. Gordon
- , Seungbyn Baek
- & Nadav Ahituv
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Article
| Open AccessMarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer
Identifying rare cell populations is key to understanding cancer progression and response to therapy. Here, authors introduce MarsGT, an end-to-end deep learning model for rare cell population identification from scMulti-omics data.
- Xiaoying Wang
- , Maoteng Duan
- & Qin Ma
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Article
| Open AccessECOLE: Learning to call copy number variants on whole exome sequencing data
Copy number variants (CNV) are shown to contribute to the etiology of various genetic disorders. Here, authors present ECOLE, a deep learning-based somatic and germline CNV caller for WES data. Utilising a variant of the transformer architecture, the model is trained to call CNVs per exon.
- Berk Mandiracioglu
- , Furkan Ozden
- & A. Ercument Cicek
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Article
| Open AccessMultiple independent losses of the biosynthetic pathway for two tropane alkaloids in the Solanaceae family
Hyoscyamine and scopolamine (HS) are two tropane alkaloids with medicinal significance produced by distantly related lineages in the Solanaceae family. Here, the authors assemble the genome of three HS-producing and one non-HS-producing species within Solanaceae, and reveal the evolution of the biosynthetic pathway.
- Jiao Yang
- , Ying Wu
- & Jianquan Liu
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Article
| Open AccessHigh resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis
The integration of single-cell and spatial data can provide a more comprehensive picture of the network of cells within the tumour microenvironment. Here the authors use a combination of single-cell and spatial technologies including 10x Xenium to characterise serial formalin-fixed, paraffin-embedded human breast cancer sections.
- Amanda Janesick
- , Robert Shelansky
- & Sarah E. B. Taylor
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Article
| Open AccessWhole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma
Current sequencing technologies can shed light on the stepwise progression of lung adenocarcinoma. Here, the authors characterize tumor progression in lung adenocarcinomas from an early stage using short and long read whole-genome sequencing, bulk and spatial transcriptomics, and epigenomics.
- Yasuhiko Haga
- , Yoshitaka Sakamoto
- & Ayako Suzuki
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Article
| Open AccessDiversity and dissemination of viruses in pathogenic protozoa
Heeren et al study the evolutionary genomics of leishmaniasis in Peru and Bolivia to show that parasite hybridization increases the prevalence, diversity and spread of viruses that have been previously associated with disease severity and treatment failure.
- Senne Heeren
- , Ilse Maes
- & Frederik Van den Broeck
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Article
| Open AccessMaternal dominance contributes to subgenome differentiation in allopolyploid fishes
Cyprinids fish species contain multiple subgenomes as a result of past duplications. Here, Xu et al. report new genomes of 21 cyprinid fish and conclude that observed subgenome dominance patterns are likely due to both maternal dominance and transposable element densities in each polyploid.
- Min-Rui-Xuan Xu
- , Zhen-Yang Liao
- & Hua-Hao Zhang
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Article
| Open AccessStructural variants involved in high-altitude adaptation detected using single-molecule long-read sequencing
Here, the authors use single-molecule long-read sequencing to decipher the role of structural variations in high-altitude adaptation, finding evidence that an intergenic deletion down-regulates EPAS1 by disrupting a super-enhancer.
- Jinlong Shi
- , Zhilong Jia
- & Kunlun He
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Article
| Open AccessTopological structures and syntenic conservation in sea anemone genomes
Slowly evolving cnidarians are useful models to study genome architecture. This study shows that sea anemones have a high degree of chromosomal macrosynteny, but poor microsynteny conservation. This is correlated with a small genome size and short distances of cis-regulatory elements to genes.
- Bob Zimmermann
- , Juan D. Montenegro
- & Ulrich Technau
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Article
| Open AccessDissecting the basis for differential substrate specificity of ADAR1 and ADAR2
Human ADAR1 and ADAR2 edit millions of adenosines transcriptome-wide, altering RNA structure. Here the authors show that variations in RNA binding domains influence site-specific editing, enhancing ADAR2-targeted therapeutics.
- Marlon S. Zambrano-Mila
- , Monika Witzenberger
- & Schraga Schwartz
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Article
| Open AccessDispersal from the Qinghai-Tibet plateau by a high-altitude butterfly is associated with rapid expansion and reorganization of its genome
The butterfly Parnassius glacialis experienced vast environmental transition when it dispersed out of the Qinghai-Tibet plateau. Here, the authors find that P. glacialis has an unusually large genome with rapid accumulation of transposable elements possibly facilitating its evolutionary adaptation.
- Youjie Zhao
- , Chengyong Su
- & Jiasheng Hao
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Article
| Open AccessRIF1 regulates early replication timing in murine B cells
Here the authors show that in activated B cells, RIF1 primarily binds early-replicating active chromatin and promotes early replication. RIF1 and MCM proteins establish early replication timing signatures genome-wide and ensure early replication of highly transcribed genes.
- Daniel Malzl
- , Mihaela Peycheva
- & Rushad Pavri
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Article
| Open AccessOutward-oriented sites within clustered CTCF boundaries are key for intra-TAD chromatin interactions and gene regulation
The TAD boundaries comprise clustered arrays of CTCF sites with complex orientations. Here the authors show that the outward-oriented CTCF sites within clustered TAD boundaries are central for intra-TAD chromatin spatial contacts and gene regulation.
- Xiao Ge
- , Haiyan Huang
- & Qiang Wu
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Article
| Open AccessJUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer’s disease
It has recently been reported a link between Alzheimer’s disease and mobilization of transposable elements (TEs) in heterochromatic regions. Here the authors demonstrate that dysregulation of the pioneer transcription factor c-JUN (AP-1) underlies aberrant transposable element mobilization, associated innate immune 2 response, and impaired neurogenesis in Alzheimer’s disease.
- Chiara Scopa
- , Samantha M. Barnada
- & Marco Trizzino
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Article
| Open AccessCell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease
Alzheimer’s disease genetic risk is enriched in glial genes. Here, the authors derive cell-type-specific polygenic risk scores and link astrocytic genes with Aβ, and microglial genes with Aβ, tau, microglial activation, and cognitive decline.
- Hyun-Sik Yang
- , Ling Teng
- & Reisa A. Sperling
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Article
| Open AccessDetection of isoforms and genomic alterations by high-throughput full-length single-cell RNA sequencing in ovarian cancer
Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.
- Arthur Dondi
- , Ulrike Lischetti
- & Niko Beerenwinkel
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Article
| Open AccessThe rate of epigenetic drift scales with maximum lifespan across mammals
Epigenetic drift has been hypothesized to contribute to epigenetic clock signals and variation in lifespan across species. Here, the authors show that an empirical measure of epigenetic drift scales with maximum lifespan across four mammal species and accumulates in non-random genomic locations.
- Emily M. Bertucci-Richter
- & Benjamin B. Parrott
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Perspective
| Open AccessMulti-omics for studying and understanding polar life
Endangered polar ecosystems play critical roles in the Earth’s climate system and comprise many different habitats with unique organisms. Here, the authors propose a community road map to use multi-omics data from polar organisms for conservation, ecosystem services and societal gain.
- M. S. Clark
- , J. I. Hoffman
- & T. Mock
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Article
| Open AccessThe metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi
Pneumococcal vaccination has been shown to promote emergence of non-vaccine S. pneumoniae serotypes. Here, the authors use data from Malawi to investigate whether vaccine introduction also results in changes in metabolic, virulence, and antimicrobial resistance profiles of circulating strains.
- Uri Obolski
- , Todd D. Swarthout
- & Robert S. Heyderman
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Article
| Open AccessTransposable element-initiated enhancer-like elements generate the subgenome-biased spike specificity of polyploid wheat
The direct impacts of transposable element dynamics on polyploid regulation and developmental specificity remain unclear. Here, the authors show that a large proportion of enhancer-like elements (ELEs) are mainly originated from RLG_famc7.3 specifically expanded in subgenome A, producing active nascent transcripts and influencing wheat spike development.
- Yilin Xie
- , Songbei Ying
- & Yijing Zhang
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Article
| Open AccessHigh-sensitive spatially resolved T cell receptor sequencing with SPTCR-seq
Understanding T cell behaviour in cancers is vital for improving immunotherapies. Here, the authors present spatially resolved T cell receptor sequencing (SPTCR-seq), a technology that annotates T cell receptors within the tumour ecosystem.
- Jasim Kada Benotmane
- , Jan Kueckelhaus
- & Dieter Henrik Heiland
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Article
| Open AccessPolyethyleneimine-coated MXene quantum dots improve cotton tolerance to Verticillium dahliae by maintaining ROS homeostasis
Verticillum wilt is an important cotton disease caused by fungal pathogen Verticillium dahiae. Here, the authors assemble the genomes of defoliating and non-defoliating isolates of the pathogen, identify virulence gene SP3, and develop a disease control strategy using polyethyleneimine-coated MXene quantum dots.
- Ping Qiu
- , Jiayue Li
- & Longfu Zhu
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Article
| Open AccessBacteria can maintain rRNA operons solely on plasmids for hundreds of millions of years
Bacteria usually have at least one rRNA operon on the chromosome, suggesting that the exclusive presence of rRNA operons on a plasmid is rare and unlikely to be stably maintained. Here, Anda et al. find that at least four bacterial clades in different phyla lost their chromosomal rRNA operons independently, and one of the clades has maintained this peculiar genome organization for hundreds of millions of years.
- Mizue Anda
- , Shun Yamanouchi
- & Wataru Iwasaki
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Article
| Open AccessMalaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal
Senegal has initiated a national sentinel surveillance program for malaria parasite genetics. Here, the authors report data from the first year of the program and use it to investigate local malaria incidence, patterns of transmission, and genetic loci under selection.
- Stephen F. Schaffner
- , Aida Badiane
- & Sarah K. Volkman
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Article
| Open AccessA statistical framework for differential pseudotime analysis with multiple single-cell RNA-seq samples
Pseudotime analysis is prevalent in single-cell RNA-seq, but it remains challenging to perform it across multiple samples and experimental conditions. Here, the authors develop Lamian, a computational framework for multi-sample pseudotime analysis that adjusts for biological and technical variation to detect gene program changes along cell trajectories and across conditions.
- Wenpin Hou
- , Zhicheng Ji
- & Hongkai Ji
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Article
| Open AccessEASTR: Identifying and eliminating systematic alignment errors in multi-exon genes
The study reveals limitations in widely used RNA-seq aligners, which create 'phantom' introns in reference databases. The authors introduce EASTR, a computational tool that not only enhances alignment accuracy but also uncovers existing annotation errors. This improvement bolsters the dependability of subsequent RNA-seq analyses.
- Ida Shinder
- , Richard Hu
- & Mihaela Pertea
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Article
| Open AccessPreneoplastic liver colonization by 11p15.5 altered mosaic cells in young children with hepatoblastoma
Paediatric liver cancer is rare, and often associated with a predisposition syndrome. Here, the authors show that 11p15.5 mosaic alteration in the liver is a pre-neoplastic lesion associated with hepatoblastoma, and spatial transcriptomics together with single-nucleus RNAseq identify a an altered zonation in the liver of these patients.
- Jill Pilet
- , Theo Z. Hirsch
- & Jessica Zucman-Rossi
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Article
| Open AccessAncestry-specific polygenic risk scores are risk enhancers for clinical cardiovascular disease assessments
Polygenic risk scores have been proposed as useful to refine cardiovascular risk assessments. Here, the authors validate polygenic risk scores in multiple ancestries and demonstrate their utility to more accurately assess 10 year risk.
- George B. Busby
- , Scott Kulm
- & Giordano Bottà
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Article
| Open AccessDiagnostic and commensal Staphylococcus pseudintermedius genomes reveal niche adaptation through parallel selection of defense mechanisms
Staphylococcus pseudintermedius has a wide host-range in domesticated and wild animals, yet it has also been isolated as an opportunistic pathogen in human wounds. In this work, the authors genotypically analyse S. pseudintermedius isolates from veterinary diagnostic laboratories and medical care centres, alongside household surfaces and inhabitants.
- Sanjam S. Sawhney
- , Rhiannon C. Vargas
- & Gautam Dantas
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Article
| Open AccessDissecting the human leptomeninges at single-cell resolution
The meninges protect the central nervous system at the brain border, and its dysfunction can lead to neural inflammation and cell damage. Here, the authors uncover the gene signatures of diverse cell types in the aged human leptomeninges and highlight their changes in Alzheimer’s Disease.
- Nicola A. Kearns
- , Artemis Iatrou
- & Yanling Wang
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Article
| Open AccessIsoform-resolved transcriptome of the human preimplantation embryo
Human embryo development involves extensive transcriptional remodeling. In this study, the authors apply long- and short-read RNA-Seq to profile the transcriptomes of 73 human preimplantation embryos spanning zygotic to blastocyst stages, identifying tens of thousands of additional isoforms transcribed from both known and unannotated gene loci.
- Denis Torre
- , Nancy J. Francoeur
- & Robert Sebra
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Article
| Open AccesseQTL mapping in fetal-like pancreatic progenitor cells reveals early developmental insights into diabetes risk
Fetal development plays an important role in defining adult diabetes risk. Here, authors identified a genetic link between fetal pancreatic gene expression, obesity, and diabetes risk through eQTL mapping of iPSC-derived pancreatic progenitor cells.
- Jennifer P. Nguyen
- , Timothy D. Arthur
- & Kelly A. Frazer
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Article
| Open AccessSystematic analysis of paralogous regions in 41,755 exomes uncovers clinically relevant variation
Chameleolyser enables the accurate identification of genetic variants hidden within complex regions of the genome. Its application uncovers the disease-explanatory variant in 25 previously undiagnosed patients.
- Wouter Steyaert
- , Lonneke Haer-Wigman
- & Christian Gilissen
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Article
| Open AccessInvasive Californian death caps develop mushrooms unisexually and bisexually
The death cap mushroom Amanita phalloides is invading California but little is known about how it spreads through forests. Wang et al. discover that this fungus can develop mushrooms and sporulate without mating; the nuclei involved in unisexuality appear to have persisted in invaded habitats for decades.
- Yen-Wen Wang
- , Megan C. McKeon
- & Anne Pringle
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Article
| Open AccessLow mutation rate in epaulette sharks is consistent with a slow rate of evolution in sharks
Mutations provide the genetic variability required for evolutionary change. Here, using pedigree-based whole genome sequencing, the authors determine that the Epaulette shark appears to have the lowest mutation rate identified in a vertebrate, providing a potential explanation for slow evolution in the shark lineage.
- Ashley T. Sendell-Price
- , Frank J. Tulenko
- & Manfred Schartl
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Article
| Open AccessClinical utility of polygenic scores for cardiometabolic disease in Arabs
Arabs account for 5% of the world population and have a high burden of cardiometabolic disease. Here, the authors optimize polygenic scores for 10 cardiometabolic traits in 5399 Arabs, achieving a performance on par with that among European-ancestry individuals.
- Injeong Shim
- , Hiroyuki Kuwahara
- & Akl C. Fahed
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Article
| Open AccessNeST: nested hierarchical structure identification in spatial transcriptomic data
A wide variety of tissues exhibit nested hierarchical organisation of cells in gene expression and activities. Here, authors present NeST, a method for spatial transcriptomics to identify such structures and uncover their functions via ligand-receptor communication, in both two and three dimensions.
- Benjamin L. Walker
- & Qing Nie
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Article
| Open AccessThe admixed brushtail possum genome reveals invasion history in New Zealand and novel imprinted genes
The brushtail possum is a treasured Australian marsupial, but also a harmful pest introduced into New Zealand. Here, using functional genomics and a new chromosome-level genome assembly of New Zealand possums, Bond et al. quantify their genome admixture and identify unique parent-specific and weaning associated gene expression.
- Donna M. Bond
- , Oscar Ortega-Recalde
- & Timothy A. Hore
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Article
| Open AccessMiniature spatial transcriptomics for studying parasite-endosymbiont relationships at the micro scale
The filarial worm Brugia malayi has evolved a mutualistic association with the endosymbiotic bacteria Wolbachia. Here, Sounart et al describe a spatial transcriptomic technique that can spatially resolve these miniature specimens.
- Hailey Sounart
- , Denis Voronin
- & Stefania Giacomello
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Article
| Open AccessSARS-CoV-2 genomic surveillance in wastewater as a model for monitoring evolution of endemic viruses
SARS-CoV-2 wastewater surveillance could provide an important means of monitoring population trends as clinical testing decreases. Here, the authors demonstrate the use of wastewater to track variants of concern through a sentinel wastewater surveillance system in South Africa.
- Mukhlid Yousif
- , Said Rachida
- & Kerrigan McCarthy
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Article
| Open AccessPhylogenomics reveals the history of host use in mosquitoes
Despite the significance of mosquitos for human health, little research has focused on their phylogeny. Here, the authors present a resolved phylogenetic history of mosquitoes based on phylogenomics showing that these major disease vectors radiated coincidentally with geologic events and the diversification of their hosts.
- John Soghigian
- , Charles Sither
- & Brian M. Wiegmann
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Article
| Open AccessTargetable NOTCH1 rearrangements in reninoma
Reninomas are very rare kidney tumours of juxtaglomerular cells. Here, the authors analyse reninomas using whole-genome and transcriptome sequencing, and reveal the presence and functional effects of NOTCH1 rearrangements.
- Taryn D. Treger
- , John E. G. Lawrence
- & Tanzina Chowdhury
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Article
| Open AccessLola-I is a promoter pioneer factor that establishes de novo Pol II pausing during development
Gene promoters are very often poised for expression by paused RNA polymerase II. Here, Ramalingam et al., identify a mechanism for the de novo establishment of paused Pol II at promoters and study its effects on expression.
- Vivekanandan Ramalingam
- , Xinyang Yu
- & Julia Zeitlinger
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Article
| Open AccessDynamics of transposable element accumulation in the non-recombining regions of mating-type chromosomes in anther-smut fungi
In the absence of recombination, the number of transposable elements (TEs) increases, but their accumulation dynamics are not well characterized. This study shows that TEs rapidly accumulated in non-recombining fungal mating-type chromosomes before reaching a plateau, possibly forming a TE reservoir.
- Marine Duhamel
- , Michael E. Hood
- & Tatiana Giraud
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Article
| Open AccessA landscape of complex tandem repeats within individual human genomes
Haplotype-resolved long, complex tandem repeats remain largely hidden despite their potential relevance to disease. Here, the authors reveal and analyze the genome-wide landscape of these repeats using a high-precision algorithm.
- Kazuki Ichikawa
- , Riki Kawahara
- & Shinichi Morishita
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Article
| Open AccessThe genomic footprint of whaling and isolation in fin whale populations
Industrial whaling drove several species to near extinction. From an analysis of 50 whole-genomes from fin whale populations, this study shows that the fin whale population in the Eastern North Pacific was reduced 99% during whaling but has maintained genomic diversity, whereas the Gulf of California population remained small and isolated, resulting in increased genetic load.
- Sergio F. Nigenda-Morales
- , Meixi Lin
- & Robert K. Wayne