I. Global gene expression profiling using DNA microarrays

2002 ◽  
Vol 282 (3) ◽  
pp. G397-G402 ◽  
Author(s):  
Mayi Arcellana-Panlilio ◽  
Stephen M. Robbins
Keyword(s):  
Dna Microarrays ◽  
Genomic Sequence ◽  
Structural Information ◽  
Global Gene Expression ◽  
Factors Affecting ◽  
Genome Wide ◽  
Specific Hybridization ◽  
A Genome ◽  
Global Gene Expression Profiling ◽  
Wide Scale

Having the complete human genomic sequence poses a new challenge: to use genomic structural information to display and analyze biological processes on a genome-wide scale to assign gene function. DNA microarrays are a miniaturized, ordered arrangement of nucleic acid fragments from individual genes located at defined positions on a solid support, enabling the analysis of thousands of genes in parallel by specific hybridization. This review describes technical aspects, discusses relevant applications, and suggests factors affecting the use of this technology and how it fits in the grand scheme of meeting the needs of the postgenomic era.

scholarly journals DNA microarrays, a novel approach in studies of chromatin structure.

2004 ◽  
Vol 51 (1) ◽  
pp. 1-8
Author(s):  
Piotr Widłak
Keyword(s):  
Gene Expression ◽  
Dna Microarray ◽  
Chromatin Structure ◽  
Expression Profiling ◽  
Genetic Information ◽  
Dna Microarrays ◽  
Microarray Technology ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale

The DNA microarray technology delivers an experimental tool that allows surveying expression of genetic information on a genome-wide scale at the level of single genes--for the new field termed functional genomics. Gene expression profiling--the primary application of DNA microarrays technology--generates monumental amounts of information concerning the functioning of genes, cells and organisms. However, the expression of genetic information is regulated by a number of factors that cannot be directly targeted by standard gene expression profiling. The genetic material of eukaryotic cells is packed into chromatin which provides the compaction and organization of DNA for replication, repair and recombination processes, and is the major epigenetic factor determining the expression of genetic information. Genomic DNA can be methylated and this modification modulates interactions with proteins which change the functional status of genes. Both chromatin structure and transcriptional activity are affected by the processes of replication, recombination and repair. Modified DNA microarray technology could be applied to genome-wide study of epigenetic factors and processes that modulate the expression of genetic information. Attempts to use DNA microarrays in studies of chromatin packing state, chromatin/DNA-binding protein distribution and DNA methylation pattern on a genome-wide scale are briefly reviewed in this paper.

scholarly journals Regulation of global transcription inE. coliby Rsd and 6S RNA

2016 ◽  
Author(s):  
Avantika Lal ◽  
Sandeep Krishna ◽  
Aswin Sai Narain Seshasayee
Keyword(s):  
Rna Polymerase ◽  
Sigma Factor ◽  
Global Gene Expression ◽  
Rna Seq ◽  
Genome Wide ◽  
A Genome ◽  
6S Rna ◽  
Wide Scale ◽  
Five Phases ◽  
First Time

ABSTRACTInEscherichia coli, the sigma factor σ70directs RNA polymerase to transcribe growth-related genes, while σ38directs transcription of stress response genes during stationary phase. Two molecules hypothesized to regulate RNA polymerase are the protein Rsd, which binds to σ70, and the non-coding 6S RNA which binds to the RNA polymerase- σ70holoenzyme. Despite multiple studies, the functions of Rsd and 6S RNA remain controversial. Here we use RNA-Seq in five phases of growth to elucidate their function on a genome-wide scale. We show for the first time that Rsd and 6S RNA facilitate σ38activity throughout bacterial growth, while 6S RNA also regulates widely different genes depending upon growth phase. We discover novel interactions between 6S RNA and Rsd and show widespread expression changes in a strain lacking both regulators. Finally, we present a mathematical model of transcription which highlights the crosstalk between Rsd and 6S RNA as a crucial factor in controlling sigma factor competition and global gene expression.

scholarly journals Incomplete MyoD-induced transdifferentiation is associated with chromatin remodeling deficiencies

2017 ◽  
Author(s):  
Dinesh Manandhar ◽  
Lingyun Song ◽  
Ami Kabadi ◽  
Jennifer Kwon ◽  
Lee Edsall ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chromatin Remodeling ◽  
Global Gene Expression ◽  
Chromatin Accessibility ◽  
Marker Genes ◽  
Target Cells ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Quantitative Analyses

Our current understanding of cellular transdifferentiation systems is limited. It is oftentimes unknown, at a genome-wide scale, how much transdifferentiated cells differ quantitatively from both the starting cells and the target cells. Focusing on transdifferentiation of primary human skin fibroblasts by forced expression of myogenic transcription factor MyoD, we performed quantitative analyses of gene expression and chromatin accessibility profiles of transdifferentiated cells compared to fibroblasts and myoblasts. In this system, we find that while many of the early muscle marker genes are reprogrammed, global gene expression and accessibility changes are still incomplete when compared to myoblasts. In addition, we find evidence of epigenetic memory in the transdifferentiated cells, with reminiscent features of fibroblasts being visible both in chromatin accessibility and gene expression. Quantitative analyses revealed a continuum of changes in chromatin accessibility induced by MyoD, and a strong correlation between chromatin-remodeling deficiencies and incomplete gene expression reprogramming. Classification analyses identified genetic and epigenetic features that distinguish reprogrammed from non-reprogrammed sites, and suggested ways to potentially improve transdifferentiation efficiency. Our approach for combining gene expression, DNA accessibility, and protein-DNA binding data to quantify and characterize the efficiency of cellular transdifferentiation on a genome-wide scale can be applied to any transdifferentiation system.

scholarly journals F-Box Genes in the Wheat Genome and Expression Profiling in Wheat at Different Developmental Stages

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1154
Author(s):  
Min Jeong Hong ◽  
Jin-Baek Kim ◽  
Yong Weon Seo ◽  
Dae Yeon Kim
Keyword(s):  
Developmental Stages ◽  
Brachypodium Distachyon ◽  
Triticum Aestivum L ◽  
Wheat Genome ◽  
Post Translational Modification ◽  
Genome Wide ◽  
A Genome ◽  
High Sequence Homology ◽  
Wide Scale

Genes of the F-box family play specific roles in protein degradation by post-translational modification in several biological processes, including flowering, the regulation of circadian rhythms, photomorphogenesis, seed development, leaf senescence, and hormone signaling. F-box genes have not been previously investigated on a genome-wide scale; however, the establishment of the wheat (Triticum aestivum L.) reference genome sequence enabled a genome-based examination of the F-box genes to be conducted in the present study. In total, 1796 F-box genes were detected in the wheat genome and classified into various subgroups based on their functional C-terminal domain. The F-box genes were distributed among 21 chromosomes and most showed high sequence homology with F-box genes located on the homoeologous chromosomes because of allohexaploidy in the wheat genome. Additionally, a synteny analysis of wheat F-box genes was conducted in rice and Brachypodium distachyon. Transcriptome analysis during various wheat developmental stages and expression analysis by quantitative real-time PCR revealed that some F-box genes were specifically expressed in the vegetative and/or seed developmental stages. A genome-based examination and classification of F-box genes provide an opportunity to elucidate the biological functions of F-box genes in wheat.

scholarly journals Genome-wide mapping of unexplored essential regions in the Saccharomyces cerevisiae genome: evidence for hidden synthetic lethal combinations in a genetic interaction network

2014 ◽  
Vol 42 (15) ◽  
pp. 9838-9853 ◽  
Author(s):  
Saeed Kaboli ◽  
Takuya Yamakawa ◽  
Keisuke Sunada ◽  
Tao Takagaki ◽  
Yu Sasano ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetic Interaction ◽  
Interaction Network ◽  
Essential Genes ◽  
Genetic Interactions ◽  
Lethal Gene ◽  
Synthetic Lethal ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale

Abstract Despite systematic approaches to mapping networks of genetic interactions in Saccharomyces cerevisiae, exploration of genetic interactions on a genome-wide scale has been limited. The S. cerevisiae haploid genome has 110 regions that are longer than 10 kb but harbor only non-essential genes. Here, we attempted to delete these regions by PCR-mediated chromosomal deletion technology (PCD), which enables chromosomal segments to be deleted by a one-step transformation. Thirty-three of the 110 regions could be deleted, but the remaining 77 regions could not. To determine whether the 77 undeletable regions are essential, we successfully converted 67 of them to mini-chromosomes marked with URA3 using PCR-mediated chromosome splitting technology and conducted a mitotic loss assay of the mini-chromosomes. Fifty-six of the 67 regions were found to be essential for cell growth, and 49 of these carried co-lethal gene pair(s) that were not previously been detected by synthetic genetic array analysis. This result implies that regions harboring only non-essential genes contain unidentified synthetic lethal combinations at an unexpectedly high frequency, revealing a novel landscape of genetic interactions in the S. cerevisiae genome. Furthermore, this study indicates that segmental deletion might be exploited for not only revealing genome function but also breeding stress-tolerant strains.

scholarly journals Machine-learning annotation of human splicing branchpoints

2016 ◽  
Author(s):  
Bethany Signal ◽  
Brian S Gloss ◽  
Marcel E Dinger ◽  
Timothy R Mercer
Keyword(s):  
Machine Learning ◽  
Learning Algorithm ◽  
Gene Splicing ◽  
Genetic Encoding ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Wide Scale ◽  
The Impact ◽  
Splicing Patterns

ABSTRACTBackgroundThe branchpoint element is required for the first lariat-forming reaction in splicing. However due to difficulty in experimentally mapping at a genome-wide scale, current catalogues are incomplete.ResultsWe have developed a machine-learning algorithm trained with empirical human branchpoint annotations to identify branchpoint elements from primary genome sequence alone. Using this approach, we can accurately locate branchpoints elements in 85% of introns in current gene annotations. Consistent with branchpoints as basal genetic elements, we find our annotation is unbiased towards gene type and expression levels. A major fraction of introns was found to encode multiple branchpoints raising the prospect that mutational redundancy is encoded in key genes. We also confirmed all deleterious branchpoint mutations annotated in clinical variant databases, and further identified thousands of clinical and common genetic variants with similar predicted effects.ConclusionsWe propose the broad annotation of branchpoints constitutes a valuable resource for further investigations into the genetic encoding of splicing patterns, and interpreting the impact of common- and disease-causing human genetic variation on gene splicing.

scholarly journals Emerging Technologies for Genome-Wide Profiling of DNA Breakage

2021 ◽  
Vol 11 ◽  
Author(s):  
Matthew J. Rybin ◽  
Melina Ramic ◽  
Natalie R. Ricciardi ◽  
Philipp Kapranov ◽  
Claes Wahlestedt ◽  
...  
Keyword(s):  
Genome Instability ◽  
Dna Double Strand Breaks ◽  
Single Nucleotide ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Genome Wide ◽  
A Genome ◽  
Wide Scale ◽  
Nucleotide Resolution ◽  
Genomic Regions

Genome instability is associated with myriad human diseases and is a well-known feature of both cancer and neurodegenerative disease. Until recently, the ability to assess DNA damage—the principal driver of genome instability—was limited to relatively imprecise methods or restricted to studying predefined genomic regions. Recently, new techniques for detecting DNA double strand breaks (DSBs) and single strand breaks (SSBs) with next-generation sequencing on a genome-wide scale with single nucleotide resolution have emerged. With these new tools, efforts are underway to define the “breakome” in normal aging and disease. Here, we compare the relative strengths and weaknesses of these technologies and their potential application to studying neurodegenerative diseases.

The Genetics and Genomics of Asthma

2018 ◽  
Vol 19 (1) ◽  
pp. 223-246 ◽  
Author(s):  
Saffron A.G. Willis-Owen ◽  
William O.C. Cookson ◽  
Miriam F. Moffatt
Keyword(s):  
Sequence Variation ◽  
Human Microbiome ◽  
Technological Advances ◽  
Genome Wide ◽  
A Genome ◽  
Wide Range ◽  
Health And Disease ◽  
Wide Scale ◽  
Genetics And Genomics ◽  
The Individual

Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis—assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale—have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.

scholarly journals Structure-based prediction of ligand–protein interactions on a genome-wide scale

2017 ◽  
Vol 114 (52) ◽  
pp. 13685-13690 ◽  
Author(s):  
Howook Hwang ◽  
Fabian Dey ◽  
Donald Petrey ◽  
Barry Honig
Keyword(s):  
Binding Site ◽  
Protein Interactions ◽  
Kinase Inhibitors ◽  
Structural Information ◽  
Structural Alignment ◽  
Scoring Function ◽  
A Genome ◽  
Small Molecule Ligands ◽  
Wide Scale ◽  
Approved Drugs

We report a template-based method, LT-scanner, which scans the human proteome using protein structural alignment to identify proteins that are likely to bind ligands that are present in experimentally determined complexes. A scoring function that rapidly accounts for binding site similarities between the template and the proteins being scanned is a crucial feature of the method. The overall approach is first tested based on its ability to predict the residues on the surface of a protein that are likely to bind small-molecule ligands. The algorithm that we present, LBias, is shown to compare very favorably to existing algorithms for binding site residue prediction. LT-scanner’s performance is evaluated based on its ability to identify known targets of Food and Drug Administration (FDA)-approved drugs and it too proves to be highly effective. The specificity of the scoring function that we use is demonstrated by the ability of LT-scanner to identify the known targets of FDA-approved kinase inhibitors based on templates involving other kinases. Combining sequence with structural information further improves LT-scanner performance. The approach we describe is extendable to the more general problem of identifying binding partners of known ligands even if they do not appear in a structurally determined complex, although this will require the integration of methods that combine protein structure and chemical compound databases.

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