Six extant species of non-human great apes are currently recognized: Sumatran and Bornean orangutans, eastern and western gorillas, and chimpanzees and bonobos 1. However, large gaps remain in our ...knowledge of fine-scale variation in hominoid morphology, behavior, and genetics, and aspects of great ape taxonomy remain in flux. This is particularly true for orangutans (genus: Pongo), the only Asian great apes and phylogenetically our most distant relatives among extant hominids 1. Designation of Bornean and Sumatran orangutans, P. pygmaeus (Linnaeus 1760) and P. abelii (Lesson 1827), as distinct species occurred in 2001 1, 2. Here, we show that an isolated population from Batang Toru, at the southernmost range limit of extant Sumatran orangutans south of Lake Toba, is distinct from other northern Sumatran and Bornean populations. By comparing cranio-mandibular and dental characters of an orangutan killed in a human-animal conflict to those of 33 adult male orangutans of a similar developmental stage, we found consistent differences between the Batang Toru individual and other extant Ponginae. Our analyses of 37 orangutan genomes provided a second line of evidence. Model-based approaches revealed that the deepest split in the evolutionary history of extant orangutans occurred ∼3.38 mya between the Batang Toru population and those to the north of Lake Toba, whereas both currently recognized species separated much later, about 674 kya. Our combined analyses support a new classification of orangutans into three extant species. The new species, Pongo tapanuliensis, encompasses the Batang Toru population, of which fewer than 800 individuals survive.
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•We describe a new species of great apes, the Tapanuli orangutan Pongo tapanuliensis•Genomic analyses corroborate morphological distinctiveness of P. tapanuliensis•P. tapanuliensis comprises the oldest evolutionary lineage in the genus Pongo•With fewer than 800 individuals, P. tapanuliensis is among the most endangered great apes
Nater et al. describe a new great ape species, the Tapanuli orangutan Pongo tapanuliensis. An isolated population from Batang Toru is highly distinct from the northern Sumatran and Bornean species, based on morphological variation, corroborated by population genomic analyses. Fewer than 800 individuals of P. tapanuliensis survive in the wild.
The use of two kinase inhibitors (2i) enables derivation of mouse embryonic stem cells (ESCs) in the pluripotent ground state. Using whole-genome bisulfite sequencing (WGBS), we show that male 2i ...ESCs are globally hypomethylated compared to conventional ESCs maintained in serum. In serum, female ESCs are hypomethyated similarly to male ESCs in 2i, and DNA methylation is further reduced in 2i. Regions with elevated DNA methylation in 2i strongly correlate with the presence of H3K9me3 on endogenous retroviruses (ERVs) and imprinted loci. The methylome of male ESCs in serum parallels postimplantation blastocyst cells, while 2i stalls ESCs in a hypomethylated, ICM-like state. WGBS analysis during adaptation of 2i ESCs to serum suggests that deposition of DNA methylation is largely random, while loss of DNA methylation during reversion to 2i occurs passively, initiating at TET1 binding sites. Together, our analysis provides insight into DNA methylation dynamics in cultured ESCs paralleling early developmental processes.
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•WGBS reveals dynamics of conversion between hypo- and hypermethylated mESC states•Maintained DNA methylation in 2i ESCs correlates with the presence of H3K9me3•The methylome of ground state 2i ESCs resembles preimplantation blastocyst cells•Hypomethylation in 2i is dependent on both inhibitors and LIF
Genome-wide DNA methylation analysis highlights changes that occur during pluripotent state transitions and identifies regions of methylation stability.
Modern horses represent heterogeneous populations specifically selected for appearance and performance. Genomic regions under high selective pressure show characteristic runs of homozygosity (ROH) ...which represent a low genetic diversity. This study aims at detecting the number and functional distribution of ROHs in different horse populations using next generation sequencing data.
Next generation sequencing was performed for two Sorraia, one Dülmen Horse, one Arabian, one Saxon-Thuringian Heavy Warmblood, one Thoroughbred and four Hanoverian. After quality control reads were mapped to the reference genome EquCab2.70. ROH detection was performed using PLINK, version 1.07 for a trimmed dataset with 11,325,777 SNPs and a mean read depth of 12. Stretches with homozygous genotypes of >40 kb as well as >400 kb were defined as ROHs. SNPs within consensus ROHs were tested for neutrality. Functional classification was done for genes annotated within ROHs using PANTHER gene list analysis and functional variants were tested for their distribution among breed or non-breed groups.
ROH detection was performed using whole genome sequences of ten horses of six populations representing various breed types and non-breed horses. In total, an average number of 3492 ROHs were detected in windows of a minimum of 50 consecutive homozygous SNPs and an average number of 292 ROHs in windows of 500 consecutive homozygous SNPs. Functional analyses of private ROHs in each horse revealed a high frequency of genes affecting cellular, metabolic, developmental, immune system and reproduction processes. In non-breed horses, 198 ROHs in 50-SNP windows and seven ROHs in 500-SNP windows showed an enrichment of genes involved in reproduction, embryonic development, energy metabolism, muscle and cardiac development whereas all seven breed horses revealed only three common ROHs in 50-SNP windows harboring the fertility-related gene YES1. In the Hanoverian, a total of 18 private ROHs could be shown to be located in the region of genes potentially involved in neurologic control, signaling, glycogen balance and reproduction. Comparative analysis of homozygous stretches common in all ten horses displayed three ROHs which were all located in the region of KITLG, the ligand of KIT known to be involved in melanogenesis, haematopoiesis and gametogenesis.
The results of this study give a comprehensive insight into the frequency and number of ROHs in various horses and their potential influence on population diversity and selection pressures. Comparisons of breed and non-breed horses suggest a significant artificial as well as natural selection pressure on reproduction performance in all types of horse populations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Here, we report DNA methylation and hydroxymethylation dynamics at nucleotide resolution using C/EBPα-enhanced reprogramming of B cells into induced pluripotent cells (iPSCs). We observed successive ...waves of hydroxymethylation at enhancers, concomitant with a decrease in DNA methylation, suggesting active demethylation. Consistent with this finding, ablation of the DNA demethylase Tet2 almost completely abolishes reprogramming. C/EBPα, Klf4, and Tfcp2l1 each interact with Tet2 and recruit the enzyme to specific DNA sites. During reprogramming, some of these sites maintain high levels of 5hmC, and enhancers and promoters of key pluripotency factors become demethylated as early as 1 day after Yamanaka factor induction. Surprisingly, methylation changes precede chromatin opening in distinct chromatin regions, including Klf4 bound sites, revealing a pioneer factor activity associated with alteration in DNA methylation. Rapid changes in hydroxymethylation similar to those in B cells were also observed during compound-accelerated reprogramming of fibroblasts into iPSCs, highlighting the generality of our observations.
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•Base-resolution profiling of DNA (hydroxy)methylation during iPSC reprogramming•Major contribution of Tet2-mediated demethylation throughout reprogramming•C/EBPα, Klf4, and Tfcp2l1 drive Tet2-mediated enhancer demethylation and activation•Klf4 induces enhancer demethylation in the absence of nucleosome repositioning
Using a highly efficient reprogramming system, Sardina et al. examined the dynamics of DNA methylation and hydroxymethylation. They found that throughout the process several transcription factors can recruit Tet2 to specific sites, leading to demethylation. Some of these sites became demethylated before chromatin opening.
Pyrosequencing is a sequencing-by-synthesis method that quantitatively monitors the real-time incorporation of nucleotides through the enzymatic conversion of released pyrophosphate into a ...proportional light signal. Quantitative measures are of special importance for DNA methylation analysis in various developmental and pathological situations. Analysis of DNA methylation patterns by pyrosequencing combines a simple reaction protocol with reproducible and accurate measures of the degree of methylation at several CpGs in close proximity with high quantitative resolution. After bisulfite treatment and PCR, the degree of each methylation at each CpG position in a sequence is determined from the ratio of T and C. The process of purification and sequencing can be repeated for the same template to analyze other CpGs in the same amplification product. Quantitative epigenotypes are obtained using this protocol in approximately 4 h for up to 96 DNA samples when bisulfite-treated DNA is already available as the starting material.
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Efficient sharing and integration of phenotypic data is crucial for advancing biomedical research and enhancing patient outcomes in precision medicine and public health. To achieve ...this, the health data community has developed standards to promote the harmonization of variable names and values. However, the use of diverse standards across different research centers can hinder progress. Here we present Convert-Pheno, an open-source software toolkit that enables the interconversion of common data models for phenotypic data such as Beacon v2 Models, CDISC-ODM, OMOP-CDM, Phenopackets v2, and REDCap. Along with the software, we have created a detailed documentation that includes information on deployment and installation.
Single-cell RNA sequencing (scRNA-seq) has significantly deepened our insights into complex tissues, with the latest techniques capable of processing tens of thousands of cells simultaneously. ...Analyzing increasing numbers of cells, however, generates extremely large data sets, extending processing time and challenging computing resources. Current scRNA-seq analysis tools are not designed to interrogate large data sets and often lack sensitivity to identify marker genes. With bigSCale, we provide a scalable analytical framework to analyze millions of cells, which addresses the challenges associated with large data sets. To handle the noise and sparsity of scRNA-seq data, bigSCale uses large sample sizes to estimate an accurate numerical model of noise. The framework further includes modules for differential expression analysis, cell clustering, and marker identification. A directed convolution strategy allows processing of extremely large data sets, while preserving transcript information from individual cells. We evaluated the performance of bigSCale using both a biological model of aberrant gene expression in patient-derived neuronal progenitor cells and simulated data sets, which underlines the speed and accuracy in differential expression analysis. To test its applicability for large data sets, we applied bigSCale to assess 1.3 million cells from the mouse developing forebrain. Its directed down-sampling strategy accumulates information from single cells into index cell transcriptomes, thereby defining cellular clusters with improved resolution. Accordingly, index cell clusters identified rare populations, such as reelin (
)-positive Cajal-Retzius neurons, for which we report previously unrecognized heterogeneity associated with distinct differentiation stages, spatial organization, and cellular function. Together, bigSCale presents a solution to address future challenges of large single-cell data sets.
Distinct DNA methylomes of newborns and centenarians Heyn, Holger; Li, Ning; Ferreira, Humberto J. ...
Proceedings of the National Academy of Sciences - PNAS,
06/2012, Letnik:
109, Številka:
26
Journal Article
Recenzirano
Odprti dostop
Human aging cannot be fully understood in terms of the constrained genetic setting. Epigenetic drift is an alternative means of explaining age-associated alterations. To address this issue, we ...performed whole-genome bisulfite sequencing (WGBS) of newborn and centenarian genomes. The centenarian DNA had a lower DNA methylation content and a reduced correlation in the methylation status of neighboring cytosine—phosphate—guanine (CpGs) throughout the genome in comparison with the more homogeneously methylated newborn DNA. The more hypomethylated CpGs observed in the centenarian DNA compared with the neonate covered all genomic compartments, such as promoters, exonic, intronic, and intergenic regions. For regulatory regions, the most hypomethylated sequences in the centenarian DNA were present mainly at CpG-poor promoters and in tissue-specific genes, whereas a greater level of DNA methylation was observed in CpG island promoters. We extended the study to a larger cohort of newborn and nonagenarian samples using a 450,000 CpG-site DNA methylation microarray that reinforced the observation of more hypomethylated DNA sequences in the advanced age group. WGBS and 450,000 analyses of middle-age individuals demonstrated DNA methylomes in the crossroad between the newborn and the nonagenarian/centenarian groups. Our study constitutes a unique DNA methylation analysis of the extreme points of human life at a single-nucleotide resolution level.
To investigate the three-dimensional (3D) genome architecture across normal B cell differentiation and in neoplastic cells from different subtypes of chronic lymphocytic leukemia and mantle cell ...lymphoma patients, here we integrate in situ Hi-C and nine additional omics layers. Beyond conventional active (A) and inactive (B) compartments, we uncover a highly-dynamic intermediate compartment enriched in poised and polycomb-repressed chromatin. During B cell development, 28% of the compartments change, mostly involving a widespread chromatin activation from naive to germinal center B cells and a reversal to the naive state upon further maturation into memory B cells. B cell neoplasms are characterized by both entity and subtype-specific alterations in 3D genome organization, including large chromatin blocks spanning key disease-specific genes. This study indicates that 3D genome interactions are extensively modulated during normal B cell differentiation and that the genome of B cell neoplasias acquires a tumor-specific 3D genome architecture.
Chronic lymphocytic leukemia is a complex and heterogeneous hematological malignancy. The advance of high-throughput multi-omics technologies has significantly influenced chronic lymphocytic leukemia ...research and paved the way for precision medicine approaches. In this review, we explore the role of machine learning in the analysis of multi-omics data in this hematological malignancy. We discuss recent literature on different machine learning models applied to single omic studies in chronic lymphocytic leukemia, with a special focus on the potential contributions to precision medicine. Finally, we highlight the recently published machine learning applications in multi-omics data in this area of research as well as their potential and limitations.
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