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1.
Methods Mol Biol ; 2519: 141-153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36066719

RESUMO

Epigenome research has employed various methods to identify the genomic location of proteins of interest, such as transcription factors and histone modifications. CUT&Tag is a recently established method used in epigenome research to determine the genomic location of proteins of interest, such as transcription factors and histone modifications. In CUT&Tag method, cells are bound and hold on concanavalin A (con A)-coated magnetic beads, then a Protein-A Tn5 transposase fusion protein cuts the genome and inserts adapter sequences nearby the target protein. Here we describe the updated CUT&Tag procedure using "home-made" con A-conjugated magnetic beads. This method is free of poor suspendability and severe aggregation, hence providing improved sensitivity.


Assuntos
Genoma , Código das Histonas , Concanavalina A , Processamento de Proteína Pós-Traducional , Fatores de Transcrição/metabolismo
2.
Methods Mol Biol ; 2519: 127-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36066718

RESUMO

Hi-C is a method that analyzes genome-wide chromatin structure using next-generation sequencer. Chromatin structure is crucial for regulating transcription or replication, and Hi-C has revealed the hierarchical chromatin structures, such as loop, domain , and compartment structures. Aberrant alteration of these structures causes disease, and a number of structural aberrations in cancer cells have been reported recently. Besides, Hi-C can identify chromosome rearrangements that frequently occurred in cancer. Therefore, Hi-C is a powerful technique to analyze epigenomic and genomic aberrations in tumorigenesis. Here we will introduce the basic protocol of Hi-C in experimental and analytical aspects.


Assuntos
Cromatina , Neoplasias , Cromatina/genética , Cromossomos , Genoma , Genômica/métodos , Humanos , Neoplasias/genética
3.
BMC Biol ; 20(1): 195, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050670

RESUMO

BACKGROUND: Ray-finned fishes (Actinopterygii) perceive their environment through a range of sensory modalities, including olfaction. Anatomical diversity of the olfactory organ suggests that olfaction is differentially important among species. To explore this topic, we studied the evolutionary dynamics of the four main gene families (OR, TAAR, ORA/VR1 and OlfC/VR2) coding for olfactory receptors in 185 species of ray-finned fishes. RESULTS: The large variation in the number of functional genes, between 28 in the ocean sunfish Mola mola and 1317 in the reedfish Erpetoichthys calabaricus, is the result of parallel expansions and contractions of the four main gene families. Several ancient and independent simplifications of the olfactory organ are associated with massive gene losses. In contrast, Polypteriformes, which have a unique and complex olfactory organ, have almost twice as many olfactory receptor genes as any other ray-finned fish. CONCLUSIONS: We document a functional link between morphology of the olfactory organ and richness of the olfactory receptor repertoire. Further, our results demonstrate that the genomic underpinning of olfaction in ray-finned fishes is heterogeneous and presents a dynamic pattern of evolutionary expansions, simplifications, and reacquisitions.


Assuntos
Neurônios Receptores Olfatórios , Receptores Odorantes , Animais , Evolução Molecular , Peixes/anatomia & histologia , Peixes/genética , Genoma , Filogenia , Receptores Odorantes/genética
4.
Genet Sel Evol ; 54(1): 57, 2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36057564

RESUMO

BACKGROUND: Compared to national evaluations, international collaboration projects further improve accuracies of estimated breeding values (EBV) by building larger reference populations or performing a joint evaluation using data (or proxy of them) from different countries. Genomic selection is increasingly adopted in beef cattle, but, to date, the benefits of including genomic information in international evaluations have not been explored. Our objective was to develop an international beef cattle single-step genomic evaluation and investigate its impact on the accuracy and bias of genomic evaluations compared to current pedigree-based evaluations. METHODS: Weaning weight records were available for 331,593 animals from seven European countries. The pedigree included 519,740 animals. After imputation and quality control, 17,607 genotypes at a density of 57,899 single nucleotide polymorphisms (SNPs) from four countries were available. We implemented two international scenarios where countries were modelled as different correlated traits: an international genomic single-step SNP best linear unbiased prediction (SNPBLUP) evaluation (ssSNPBLUPINT) and an international pedigree-based BLUP evaluation (PBLUPINT). Two national scenarios were implemented for pedigree and genomic evaluations using only nationally submitted phenotypes and genotypes. Accuracies, level and dispersion bias of EBV of animals born from 2014 onwards, and increases in population accuracies were estimated using the linear regression method. RESULTS: On average across countries, 39 and 17% of sires and maternal-grand-sires with recorded (grand-)offspring across two countries were genotyped. ssSNPBLUPINT showed the highest accuracies of EBV and, compared to PBLUPINT, led to increases in population accuracy of 13.7% for direct EBV, and 25.8% for maternal EBV, on average across countries. Increases in population accuracies when moving from national scenarios to ssSNPBLUPINT were observed for all countries. Overall, ssSNPBLUPINT level and dispersion bias remained similar or slightly reduced compared to PBLUPINT and national scenarios. CONCLUSIONS: International single-step SNPBLUP evaluations are feasible and lead to higher population accuracies for both large and small countries compared to current international pedigree-based evaluations and national evaluations. These results are likely related to the larger multi-country reference population and the inclusion of phenotypes from relatives recorded in other countries via single-step international evaluations. The proposed international single-step approach can be applied to other traits and breeds.


Assuntos
Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Genoma , Genótipo , Linhagem , Fenótipo , Desmame
5.
BMC Bioinformatics ; 23(1): 364, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064314

RESUMO

BACKGROUND: Pathogenic mutations in genes that control chromatin function have been implicated in rare genetic syndromes. These chromatin modifiers exhibit extraordinary diversity in the scale of the epigenetic changes they affect, from single basepair modifications by DNMT1 to whole genome structural changes by PRM1/2. Patterns of DNA methylation are related to a diverse set of epigenetic features across this full range of epigenetic scale, making DNA methylation valuable for mapping regions of general epigenetic dysregulation. However, existing methods are unable to accurately identify regions of differential methylation across this full range of epigenetic scale directly from DNA methylation data. RESULTS: To address this, we developed DMRscaler, a novel method that uses an iterative windowing procedure to capture regions of differential DNA methylation (DMRs) ranging in size from single basepairs to whole chromosomes. We benchmarked DMRscaler against several DMR callers in simulated and natural data comparing XX and XY peripheral blood samples. DMRscaler was the only method that accurately called DMRs ranging in size from 100 bp to 1 Mb (pearson's r = 0.94) and up to 152 Mb on the X-chromosome. We then analyzed methylation data from rare-disease cohorts that harbor chromatin modifier gene mutations in NSD1, EZH2, and KAT6A where DMRscaler identified novel DMRs spanning gene clusters involved in development. CONCLUSION: Taken together, our results show DMRscaler is uniquely able to capture the size of DMR features across the full range of epigenetic scale and identify novel, co-regulated regions that drive epigenetic dysregulation in human disease.


Assuntos
Metilação de DNA , Epigênese Genética , Cromatina , Epigenômica , Genoma , Humanos
6.
Nat Commun ; 13(1): 4887, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068211

RESUMO

Wild yak (Bos mutus) and domestic yak (Bos grunniens) are adapted to high altitude environment and have ecological, economic, and cultural significances on the Qinghai-Tibetan Plateau (QTP). Currently, the genetic and cellular bases underlying adaptations of yak to extreme conditions remains elusive. In the present study, we assembled two chromosome-level genomes, one each for wild yak and domestic yak, and screened structural variants (SVs) through the long-read data of yak and taurine cattle. The results revealed that 6733 genes contained high-FST SVs. 127 genes carrying special type of SVs were differentially expressed in lungs of the taurine cattle and yak. We then constructed the first single-cell gene expression atlas of yak and taurine cattle lung tissues and identified a yak-specific endothelial cell subtype. By integrating SVs and single-cell transcriptome data, we revealed that the endothelial cells expressed the highest proportion of marker genes carrying high-FST SVs in taurine cattle lungs. Furthermore, we identified pathways which were related to the medial thickness and formation of elastic fibers in yak lungs. These findings provide new insights into the high-altitude adaptation of yak and have important implications for understanding the physiological and pathological responses of large mammals and humans to hypoxia.


Assuntos
Células Endoteliais , Genoma , Aclimatação/genética , Animais , Bovinos , Humanos , Mamíferos/genética , RNA , Transcriptoma/genética
7.
Nat Commun ; 13(1): 5255, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068235

RESUMO

CRISPR technology is a powerful tool for studying genome function. To aid in picking sgRNAs that have maximal efficacy against a target of interest from many possible options, several groups have developed models that predict sgRNA on-target activity. Although multiple tracrRNA variants are commonly used for screening, no existing models account for this feature when nominating sgRNAs. Here we develop an on-target model, Rule Set 3, that makes optimal predictions for multiple tracrRNA variants. We validate Rule Set 3 on a new dataset of sgRNAs tiling essential and non-essential genes, demonstrating substantial improvement over prior prediction models. By analyzing the differences in sgRNA activity between tracrRNA variants, we show that Pol III transcription termination is a strong determinant of sgRNA activity. We expect these results to improve the performance of CRISPR screening and inform future research on tracrRNA engineering and sgRNA modeling.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , RNA Guia , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Genoma , RNA Guia/genética , Transcrição Genética
8.
Sci Rep ; 12(1): 14984, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056154

RESUMO

Research on working dogs is growing rapidly due to increasing global demand. Here we report genome scanning of the risk of puppies being eliminated for behavioral reasons prior to entering the training phase of the US Transportation Security Administration's (TSA) canine olfactory detection breeding and training program through 2013. Elimination of dogs for behavioral rather than medical reasons was based on evaluations at three, six, nine and twelve months after birth. Throughout that period, the fostered dogs underwent standardized behavioral tests at TSA facilities, and, for a subset of tests, dogs were tested in four different environments. Using methods developed for family studies, we performed a case-control genome wide association study (GWAS) of elimination due to behavioral observation and testing results in a cohort of 528 Labrador Retrievers (2002-2013). We accounted for relatedness by including the pedigree as a covariate and maximized power by including individuals with phenotype, but not genotype, data (approximately half of this cohort). We determined genome wide significance based on Bonferroni adjustment of two quasi-likelihood score tests optimized for either small or nearly-fully penetrant effect sizes. Six loci were significant and five suggestive, with approximately equal numbers of loci for the two tests and frequencies of loci with single versus multiple mapped markers. Several loci implicate a single gene, including CHD2, NRG3 and PDE1A which have strong relevance to behavior in humans and other species. We briefly discuss how expanded studies of canine breeding programs could advance understanding of learning and performance in the mammalian life course. Although human interactions and other environmental conditions will remain critical, our findings suggest genomic breeding selection could help improve working dog populations.


Assuntos
Cruzamento , Estudo de Associação Genômica Ampla , Animais , Cães , Genoma , Genótipo , Humanos , Mamíferos , Linhagem
9.
Methods Cell Biol ; 172: 51-66, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36064226

RESUMO

Micronuclei are common byproducts of chromosomally unstable cancer cells during their division. Micronuclei play an important role in cancer metastasis as well as introducing chromosomal abnormalities into the primary nucleus in the subsequent cell cycle. Given their major role in tumor initiation and progression, methods to examine their properties are crucially needed. This chapter discusses approaches and methods to profile micronuclei's biochemical, genomic, and epigenomic properties following their physical isolation. Using either MPS1 inhibition or radiation to induce formation of micronuclei, this method introduces a versatile way to investigate biological events that occur in micronuclei as well as compare them to events in the primary nuclei from the same system.


Assuntos
Epigenômica , Neoplasias , Linhagem Celular , Genoma , Genômica , Humanos , Neoplasias/genética
10.
BMC Genomics ; 23(1): 628, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050638

RESUMO

BACKGROUND: Spliceosomal introns are parts of primary transcripts that are removed by RNA splicing. Although introns apparently do not contribute to the function of the mature transcript, in vertebrates they comprise the majority of the transcribed region increasing the metabolic cost of transcription. The persistence of long introns across evolutionary time suggests functional roles that can offset this metabolic cost. The teleosts comprise one of the largest vertebrate clades. They have unusually compact and variable genome sizes and provide a suitable system for analysing intron evolution. RESULTS: We have analysed intron lengths in 172 vertebrate genomes and show that teleost intron lengths are relatively short, highly variable and bimodally distributed. Introns that were long in teleosts were also found to be long in mammals and were more likely to be found in regulatory genes and to contain conserved sequences. Our results argue that intron length has decreased in parallel in a non-random manner throughout teleost evolution and represent a deviation from the ancestral state. CONCLUSION: Our observations indicate an accelerated rate of intron size evolution in the teleosts and that teleost introns can be divided into two classes by their length. Teleost intron sizes have evolved primarily as a side-effect of genome size evolution and small genomes are dominated by short introns (<256 base pairs). However, a non-random subset of introns has resisted this process across the teleosts and these are more likely have functional roles in all vertebrate clades.


Assuntos
Evolução Molecular , Genoma , Animais , Éxons , Íntrons/genética , Mamíferos/genética , Vertebrados/genética
11.
Genome Biol ; 23(1): 183, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050782

RESUMO

BACKGROUND: Crop improvement through cross-population genomic prediction and genome editing requires identification of causal variants at high resolution, within fewer than hundreds of base pairs. Most genetic mapping studies have generally lacked such resolution. In contrast, evolutionary approaches can detect genetic effects at high resolution, but they are limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Here we use genomic annotations to accurately predict nucleotide conservation across angiosperms, as a proxy for fitness effect of mutations. RESULTS: Using only sequence analysis, we annotate nonsynonymous mutations in 25,824 maize gene models, with information from bioinformatics and deep learning. Our predictions are validated by experimental information: within-species conservation, chromatin accessibility, and gene expression. According to gene ontology and pathway enrichment analyses, predicted nucleotide conservation points to genes in central carbon metabolism. Importantly, it improves genomic prediction for fitness-related traits such as grain yield, in elite maize panels, by stringent prioritization of fewer than 1% of single-site variants. CONCLUSIONS: Our results suggest that predicting nucleotide conservation across angiosperms may effectively prioritize sites most likely to impact fitness-related traits in crops, without being limited by shifting selection, missing data, and low depth of multiple-sequence alignments. Our approach-Prediction of mutation Impact by Calibrated Nucleotide Conservation (PICNC)-could be useful to select polymorphisms for accurate genomic prediction, and candidate mutations for efficient base editing. The trained PICNC models and predicted nucleotide conservation at protein-coding SNPs in maize are publicly available in CyVerse ( https://doi.org/10.25739/hybz-2957 ).


Assuntos
Genômica , Zea mays , Genoma , Genômica/métodos , Nucleotídeos , Fenótipo , Polimorfismo de Nucleotídeo Único , Zea mays/genética
12.
Nat Commun ; 13(1): 5281, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36075900

RESUMO

The 3D genome has been shown to be organized into modules including topologically associating domains (TADs) and compartments that are primarily defined by spatial contacts from Hi-C. There exists a gap to investigate whether and how the spatial modularity of the chromatin is related to the functional modularity resulting from chromatin activity. Despite histone modifications reflecting chromatin activity, inferring spatial modularity of the genome directly from the histone modification patterns has not been well explored. Here, we report that histone modifications show a modular pattern (referred to as regulation associated modules, RAMs) that reflects spatial chromatin modularity. Enhancer-promoter interactions, loop anchors, super-enhancer clusters and extrachromosomal DNAs (ecDNAs) are found to occur more often within the same RAMs than within the same TADs. Consistently, compared to the TAD boundaries, deletions of RAM boundaries perturb the chromatin structure more severely (may even cause cell death) and somatic variants in cancer samples are more enriched in RAM boundaries. These observations suggest that RAMs reflect a modular organization of the 3D genome at a scale better aligned with chromatin activity, providing a bridge connecting the structural and functional modularity of the genome.


Assuntos
Cromatina , Genoma , Cromatina/genética , Montagem e Desmontagem da Cromatina/genética , Cromossomos , Regiões Promotoras Genéticas/genética
13.
Sci Rep ; 12(1): 15629, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115864

RESUMO

Cancer subtypes identification is one of the critical steps toward advancing personalized anti-cancerous therapies. Accumulation of a massive amount of multi-platform omics data measured across the same set of samples provides an opportunity to look into this deadly disease from several views simultaneously. Few integrative clustering approaches are developed to capture shared information from all the views to identify cancer subtypes. However, they have certain limitations. The challenge here is identifying the most relevant feature space from each omic view and systematically integrating them. Both the steps should lead toward a global clustering solution with biological significance. In this respect, a novel multi-omics clustering algorithm named RISynG (Recursive Integration of Synergised Graph-representations) is presented in this study. RISynG represents each omic view as two representation matrices that are Gramian and Laplacian. A parameterised combination function is defined to obtain a synergy matrix from these representation matrices. Then a recursive multi-kernel approach is applied to integrate the most relevant, shared, and complementary information captured via the respective synergy matrices. At last, clustering is applied to the integrated subspace. RISynG is benchmarked on five multi-omics cancer datasets taken from The Cancer Genome Atlas. The experimental results demonstrate RISynG's efficiency over the other approaches in this domain.


Assuntos
Neoplasias , Algoritmos , Análise por Conglomerados , Genoma , Humanos , Neoplasias/genética
14.
Sci Rep ; 12(1): 15627, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115919

RESUMO

Latent class analysis (LCA) is a type of modeling analysis approach that has been used to identify unobserved groups or subgroups within multivariate categorical data. LCA has been used for a wide array of psychological evaluations in humans, including the identification of depression subtypes or PTSD comorbidity patterns. However, it has never been used for the assessment of animal behavior. Our objective here is to identify behavioral profile-types of dogs using LCA. The LCA was performed on a C-BARQ behavioral questionnaire dataset from 57,454 participants representing over 350 pure breeds and mixed breed dogs. Two, three, and four class LCA models were developed using C-BARQ trait scores and environmental covariates. In our study, LCA is shown as an effective and flexible tool to classify behavioral assessments. By evaluating the traits that carry the strongest relevance, it was possible to define the basis of these grouping differences. Groupings can be ranked and used as levels for simplified comparisons of complex constructs, such as temperament, that could be further exploited in downstream applications such as genomic association analyses. We propose this approach will facilitate dissection of physiological and environmental factors associated with psychopathology in dogs, humans, and mammals in general.


Assuntos
Comportamento Animal , Temperamento , Animais , Cruzamento , Cães , Genoma , Humanos , Análise de Classes Latentes , Mamíferos
15.
Trop Anim Health Prod ; 54(5): 295, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36100772

RESUMO

The aim of the present study was to use different models that include body composition phenotypes for the evaluation of residual feed intake (RFI) in Nellore bulls of different ages. Phenotypic and genotypic data of bulls that had participated in feed efficiency tests of a commercial (COM) and an experimental (EXP) herd between 2007 and 2019 were used. The mean entry age in the two herds was 645 and 279 days, respectively. The phenotypes were evaluated: rib eye area (REA), backfat thickness (BFT), residual feed intake (RFIKOCH), RFI adjusted for REA (RFIREA), RFI adjusted for BFT (RFIBFT), and RFI adjusted for REA and BFT (RFIREA BFT). The (co)variance components and prediction of genomic estimated breeding values (GEBV) were obtained by REML using ssGBLUP in single and two-trait analyses. Spearman's correlations were calculated based on the GEBV for RFIKOCH. The RFI phenotypes exhibited moderate heritability estimates in both herds (0.17 ± 0.03 to 0.27 ± 0.04). The genetic correlation between phenotypes was positive and high (0.99) in the two herds, a fact that permitted the creation of a single database (SDB). The heritability estimates of the SDB were also of moderate magnitude for the different definitions of RFI (0.19 ± 0.04 to 0.21 ± 0.04). The genetic correlations were positive and high between RFI traits 0.97 ± 0.01 to 0.99 ± 0.01), and positive and low/moderate between REA and BFT (0.01 ± 0.10 to 0.31 ± 0.12). The selection of animals based on the GEBV for RFIKOCH did not alter the ranking of individuals selected for RFIREA, RFIBFT, and RFIREA BFT. The results of the present study suggest that records of Nellore bulls of different ages and with different body compositions can be combined in a SDB for RFI calculation. Therefore, young animals can be evaluated in feed efficiency tests in order to reduce costs and the generation interval and possibly to obtain a higher response to selection.


Assuntos
Composição Corporal , Ingestão de Alimentos , Animais , Bovinos/genética , Ingestão de Alimentos/genética , Genoma , Masculino , Fenótipo , Costelas
16.
Gigascience ; 112022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106701

RESUMO

BACKGROUND: Asian arowana, Scleropages formosus, is one of the most expensive aquarium fish species worldwide. Its sex, however, cannot be distinguished clearly at any development stage, which impedes captive breeding and species protection for this endangered aquarium fish. RESULTS: To discover molecular clues to the sex of Asian arowana, we sequenced 26.5 Gb of PacBio HiFi reads and 179.2 Gb of Hi-C reads for 1 male fish and also sequenced 106.5 Gb of Illumina reads, 36.0 Gb of PacBio Sequel reads, and 80.7 Gb of Hi-C reads for 1 female individual. The final male and female genome assemblies were approximately 756.8 Mb and 781.5 Mb in length and contained 25,262 and 25,328 protein-coding genes, respectively. We also resequenced the genomes of 15 male and 15 female individuals with approximately 722.1 Gb of Illumina reads. A genome-wide association study identified several potentially divergent regions between male and female individuals. In these regions, cd48 and cfap52 could be candidate genes for sex determination of Asian arowana. We also found some structural variations in few chromosomes between male and female individuals. CONCLUSION: We provided an improved reference genome assembly of female arowana and generated the first sequenced genome of 1 male individual. These valuable genetic resources and resequencing data may improve global aquarium fish research.


Assuntos
Estudo de Associação Genômica Ampla , Genoma , Animais , Cromossomos , Feminino , Peixes/genética , Genômica , Masculino
17.
Nat Commun ; 13(1): 5326, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36088375

RESUMO

Trypanosomatids, which include major pathogens of humans and livestock, are flagellated protozoa for which cell cycle controls and the underlying mechanisms are not completely understood. Here, we describe a genome-wide RNA-interference library screen for cell cycle defects in Trypanosoma brucei. We induced massive parallel knockdown, sorted the perturbed population using high-throughput flow cytometry, deep-sequenced RNAi-targets from each stage and digitally reconstructed cell cycle profiles at a genomic scale; also enabling data visualisation using an online tool ( https://tryp-cycle.pages.dev/ ). Analysis of several hundred genes that impact cell cycle progression reveals >100 flagellar component knockdowns linked to genome endoreduplication, evidence for metabolic control of the G1-S transition, surface antigen regulatory mRNA-binding protein knockdowns linked to G2M accumulation, and a putative nucleoredoxin required for both mitochondrial genome segregation and for mitosis. The outputs provide comprehensive functional genomic evidence for the known and novel machineries, pathways and regulators that coordinate trypanosome cell cycle progression.


Assuntos
Trypanosoma brucei brucei , Ciclo Celular/genética , Genoma , Humanos , Mitose , Interferência de RNA , Trypanosoma brucei brucei/metabolismo
18.
PLoS One ; 17(9): e0265557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36084090

RESUMO

A common issue affecting DNA methylation analysis in tumor tissue is the presence of a substantial amount of non-tumor methylation signal derived from the surrounding microenvironment. Although approaches for quantifying and correcting for the infiltration component have been proposed previously, we believe these have not fully addressed the issue in a comprehensive and universally applicable way. We present a multi-population framework for adjusting DNA methylation beta values on the Illumina 450/850K platform using generic purity estimates to account for non-tumor signal. Our approach also provides an indirect estimate of the aggregate methylation state of the surrounding normal tissue. Using whole exome sequencing derived purity estimates and Illumina 450K methylation array data generated by The Cancer Genome Atlas project (TCGA), we provide a demonstration of this framework in breast cancer illustrating the effect of beta correction on the aggregate methylation beta value distribution, clustering accuracy, and global methylation profiles.


Assuntos
Neoplasias da Mama , Metilação de DNA , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Contagem de Células , Ilhas de CpG , Feminino , Genoma , Humanos , Microambiente Tumoral
19.
PLoS One ; 17(9): e0274414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36112576

RESUMO

The most important information about microorganisms might be their accurate genome sequence. Using current Next Generation Sequencing methods, sequencing data can be generated at an unprecedented pace. However, we still lack tools for the automated and accurate reference-based genotyping of viral sequencing reads. This paper presents our pipeline designed to reconstruct the dominant consensus genome of viral samples and analyze their within-host variability. We benchmarked our approach on numerous datasets and showed that the consensus genome of samples could be obtained reliably without further manual data curation. Our pipeline can be a valuable tool for fast identifying viral samples. The pipeline is publicly available on the project's GitHub page (https://github.com/laczkol/QVG).


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Software , Genoma , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos
20.
Sci Adv ; 8(37): eabl4642, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112682

RESUMO

Limb regeneration is a fascinating and medically interesting trait that has been well preserved in arthropod lineages, particularly in crustaceans. However, the molecular mechanisms underlying arthropod limb regeneration remain largely elusive. The Chinese mitten crab Eriocheir sinensis shows strong regenerative capacity, a trait that has likely allowed it to become a worldwide invasive species. Here, we report a chromosome-level genome of E. sinensis as well as large-scale transcriptome data during the limb regeneration process. Our results reveal that arthropod-specific genes involved in signal transduction, immune response, histone methylation, and cuticle development all play fundamental roles during the regeneration process. Particularly, Innexin2-mediated signal transduction likely facilitates the early stage of the regeneration process, while an effective crustacean-specific prophenoloxidase system (ProPo-AS) plays crucial roles in the initial immune response. Collectively, our findings uncover novel genetic pathways pertaining to arthropod limb regeneration and provide valuable resources for studies on regeneration from a comparative perspective.


Assuntos
Histonas , Transcriptoma , China , Genoma , Histonas/genética , Regeneração/genética
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