scholarly journals Generic Repeat Finder: A High-Sensitivity Tool for Genome-Wide De Novo Repeat Detection

2019 ◽  
Vol 180 (4) ◽  
pp. 1803-1815 ◽  
Author(s):  
Jieming Shi ◽  
Chun Liang
Keyword(s):  
De Novo ◽  
High Sensitivity ◽  
Genome Wide ◽  
Repeat Detection

scholarly journals Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Jing-dong Zhou ◽  
Ting-juan Zhang ◽  
Zi-jun Xu ◽  
Zhao-qun Deng ◽  
Yu Gu ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Myelodysplastic Syndromes ◽  
Bisulfite Sequencing ◽  
De Novo ◽  
Dna Hypermethylation ◽  
Reduced Representation ◽  
Targeted Bisulfite Sequencing ◽  
Specific Pcr ◽  
Genome Wide ◽  
Potential Biomarker

AbstractThe potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.

scholarly journals Enhanced specificity of clinical high-sensitivity tumor mutation profiling in cell-free DNA via paired normal sequencing using MSK-ACCESS

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
A. Rose Brannon ◽  
Gowtham Jayakumaran ◽  
Monica Diosdado ◽  
Juber Patel ◽  
Anna Razumova ◽  
...  
Keyword(s):  
Cancer Patients ◽  
De Novo ◽  
Low Frequency ◽  
High Sensitivity ◽  
Clinical Analysis ◽  
De Novo Mutation ◽  
Cell Free Dna ◽  
Free Dna ◽  
Somatic Alterations ◽  
Mutation Profiling

AbstractCirculating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.

scholarly journals A genome-wide study of de novo deletions identifies a candidate locus for non-syndromic isolated cleft lip/palate risk

BMC Genetics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 24 ◽  
Author(s):  
Samuel G Younkin ◽  
Robert B Scharpf ◽  
Holger Schwender ◽  
Margaret M Parker ◽  
Alan F Scott ◽  
...  
Keyword(s):  
Cleft Lip ◽  
De Novo ◽  
Candidate Locus ◽  
Genome Wide ◽  
A Genome ◽  
Cleft Lip Palate ◽  
Genome Wide Study

scholarly journals Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns

2021 ◽  
Author(s):  
Yannik Bollen ◽  
Ellen Stelloo ◽  
Petra van Leenen ◽  
Myrna van den Bos ◽  
Bas Ponsioen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Cell ◽  
Temporal Dynamics ◽  
De Novo ◽  
Tumor Evolution ◽  
Genome Wide ◽  
Aneuploid Tumor ◽  
Evolutionary Paths ◽  
Tumor Biopsies ◽  
Punctuated Evolution

AbstractCentral to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.

Bacterial origin of thymidylate and folate metabolism in Asgard Archaea

2021 ◽  
Author(s):  
Jonathan Filee ◽  
Hubert J. Becker ◽  
Lucille Mellottee ◽  
Zhihui LI ◽  
Jean-Christophe Lambry ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Lateral Gene Transfer ◽  
Phylogenetic Trees ◽  
De Novo ◽  
Horizontal Transmission ◽  
Folate Metabolism ◽  
Ecological Niches ◽  
Sequence Information ◽  
Amino Acid Utilization ◽  
Genome Wide

Little is known about the evolution and biosynthetic function of DNA precursor and the folate metabolism in the Asgard group of archaea. As Asgard occupy a key position in the archaeal and eukaryotic phylogenetic trees, we have exploited very recently emerged genome and metagenome sequence information to investigate these central metabolic pathways. Our genome-wide analyses revealed that the recently cultured Asgard archaeon Candidatus Prometheoarchaeum syntrophicum strain MK-D1 (Psyn) contains a complete folate-dependent network for the biosynthesis of DNA/RNA precursors, amino acids and syntrophic amino acid utilization. Altogether our experimental and computational data suggest that phylogenetic incongruences of functional folate-dependent enzymes from Asgard archaea reflect their persistent horizontal transmission from various bacterial groups, which has rewired the key metabolic reactions in an important and recently identified archaeal phylogenetic group. We also experimentally validated the functionality of the lateral gene transfer of Psyn thymidylate synthase ThyX. This enzyme uses bacterial-like folates efficiently and is inhibited by mycobacterial ThyX inhibitors. Our data raise the possibility that the thymidylate metabolism, required for de novo DNA synthesis, originated in bacteria and has been independently transferred to archaea and eukaryotes. In conclusion, our study has revealed that recent prevalent lateral gene transfer has markedly shaped the evolution of Asgard archaea by allowing them to adapt to specific ecological niches.

scholarly journals Gene-specific mechanisms direct glucocorticoid-receptor-driven repression of inflammatory response genes in macrophages

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Maria A Sacta ◽  
Bowranigan Tharmalingam ◽  
Maddalena Coppo ◽  
David A Rollins ◽  
Dinesh K Deochand ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Binding Sites ◽  
De Novo ◽  
Elongation Factor ◽  
Myeloid Cell ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
Mouse Macrophages ◽  
Underlying Mechanisms ◽  
Temporal Events

The glucocorticoid receptor (GR) potently represses macrophage-elicited inflammation, however, the underlying mechanisms remain obscure. Our genome-wide analysis in mouse macrophages reveals that pro-inflammatory paused genes, activated via global negative elongation factor (NELF) dissociation and RNA Polymerase (Pol)2 release from early elongation arrest, and non-paused genes, induced by de novo Pol2 recruitment, are equally susceptible to acute glucocorticoid repression. Moreover, in both cases the dominant mechanism involves rapid GR tethering to p65 at NF-kB-binding sites. Yet, specifically at paused genes, GR activation triggers widespread promoter accumulation of NELF, with myeloid cell-specific NELF deletion conferring glucocorticoid resistance. Conversely, at non-paused genes, GR attenuates the recruitment of p300 and histone acetylation, leading to a failure to assemble BRD4 and Mediator at promoters and enhancers, ultimately blocking Pol2 initiation. Thus, GR displays no preference for a specific pro-inflammatory gene class; however, it effects repression by targeting distinct temporal events and components of transcriptional machinery.

scholarly journals Genotypic and Phenotypic Characterization of Lettuce Bacterial Pathogen Xanthomonas hortorum pv. vitians Populations Collected in Quebec, Canada

Agronomy ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2386
Author(s):  
Pierre-Olivier Hébert ◽  
Martin Laforest ◽  
Dong Xu ◽  
Marie Ciotola ◽  
Mélanie Cadieux ◽  
...  
Keyword(s):  
Leaf Spot ◽  
Genome Wide Association Study ◽  
De Novo ◽  
Association Studies ◽  
Genome Wide Association ◽  
Phenotypic Characterization ◽  
Genome Wide Association Studies ◽  
Bacterial Leaf Spot ◽  
Eastern Canada ◽  
Genome Wide

Bacterial leaf spot of lettuce, caused by Xanthomonas hortorum pv. vitians, is an economically important disease worldwide. For instance, it caused around 4 million CAD in losses in only a few months during the winter of 1992 in Florida. Because only one pesticide is registered to control this disease in Canada, the development of lettuce cultivars tolerant to bacterial leaf spot remains the most promising approach to reduce the incidence and severity of the disease in lettuce fields. The lack of information about the genetic diversity of the pathogen, however, impairs breeding programs, especially when disease resistance is tested on newly developed lettuce germplasm lines. To evaluate the diversity of X. hortorum pv. vitians, a multilocus sequence analysis was performed on 694 isolates collected in Eastern Canada through the summers of 2014 to 2017 and two isolates in 1996 and 2007. All isolates tested were clustered into five phylogroups. Six pathotypes were identified following pathogenicity tests conducted in greenhouses, but when phylogroups were compared with pathotypes, no correlation could be drawn. However, in vitro production of xanthan and xanthomonadins was investigated, and isolates with higher production of xanthomonadins were generally causing less severe symptoms on the tolerant cultivar Little Gem. Whole-genome sequencing was undertaken for 95 isolates belonging to the pathotypes identified, and de novo assembly made with reads unmapped to the reference strain’s genome sequence resulted in 694 contigs ranging from 128 to 120,795 bp. Variant calling was performed prior to genome-wide association studies computed with single-nucleotide polymorphisms (SNPs), copy-number variants and gaps. Polymorphisms with significant p-values were only found on the cultivar Little Gem. Our results allowed molecular identification of isolates likely to cause bacterial leaf spot of lettuce, using two SNPs identified through genome-wide association study.

scholarly journals Genome assembly of the JD17 soybean provides a new reference genome for Comparative genomics

2021 ◽  
Author(s):  
Xinxin Yi ◽  
Jing Liu ◽  
Shengcai Chen ◽  
Hao Wu ◽  
Min Liu ◽  
...  
Keyword(s):  
Nitrogen Fixation ◽  
Genome Assembly ◽  
Reference Genome ◽  
De Novo ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
High Quality ◽  
Genome Wide ◽  
A Genome ◽  
Cultivated Soybean

Cultivated soybean (Glycine max) is an important source for protein and oil. Many elite cultivars with different traits have been developed for different conditions. Each soybean strain has its own genetic diversity, and the availability of more high-quality soybean genomes can enhance comparative genomic analysis for identifying genetic underpinnings for its unique traits. In this study, we constructed a high-quality de novo assembly of an elite soybean cultivar Jidou 17 (JD17) with chromsome contiguity and high accuracy. We annotated 52,840 gene models and reconstructed 74,054 high-quality full-length transcripts. We performed a genome-wide comparative analysis based on the reference genome of JD17 with three published soybeans (WM82, ZH13 and W05) , which identified five large inversions and two large translocations specific to JD17, 20,984 - 46,912 PAVs spanning 13.1 - 46.9 Mb in size, and 5 - 53 large PAV clusters larger than 500kb. 1,695,741 - 3,664,629 SNPs and 446,689 - 800,489 Indels were identified and annotated between JD17 and them. Symbiotic nitrogen fixation (SNF) genes were identified and the effects from these variants were further evaluated. It was found that the coding sequences of 9 nitrogen fixation-related genes were greatly affected. The high-quality genome assembly of JD17 can serve as a valuable reference for soybean functional genomics research.

scholarly journals Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO)

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1449
Author(s):  
Luca M. Schierbaum ◽  
Sophia Schneider ◽  
Stefan Herms ◽  
Sugirthan Sivalingam ◽  
Julia Fabian ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Lower Urinary Tract ◽  
De Novo ◽  
Urinary Tract Obstruction ◽  
Posterior Urethral Valves ◽  
Rare Cnvs ◽  
Genome Wide ◽  
Lower Urinary Tract Obstruction ◽  
Human Specific ◽  
Lower Urinary

Lower urinary tract obstruction (LUTO) is, in most cases, caused by anatomical blockage of the bladder outlet. The most common form are posterior urethral valves (PUVs), a male-limited phenotype. Here, we surveyed the genome of 155 LUTO patients to identify disease-causing CNVs. Raw intensity data were collected for CNVs detected in LUTO patients and 4.392 healthy controls using CNVPartition, QuantiSNP and PennCNV. Overlapping CNVs between patients and controls were discarded. Additional filtering implicated CNV frequency in the database of genomic variants, gene content and final visual inspection detecting 37 ultra-rare CNVs. After, prioritization qPCR analysis confirmed 3 microduplications, all detected in PUV patients. One microduplication (5q23.2) occurred de novo in the two remaining microduplications found on chromosome 1p36.21 and 10q23.31. Parental DNA was not available for segregation analysis. All three duplications comprised 11 coding genes: four human specific lncRNA and one microRNA. Three coding genes (FBLIM1, SLC16A12, SNCAIP) and the microRNA MIR107 have previously been shown to be expressed in the developing urinary tract of mouse embryos. We propose that duplications, rare or de novo, contribute to PUV formation, a male-limited phenotype.

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