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Most Cited Genomics, Proteomics & Bioinformatics Articles
The most cited articles published since 2010, extracted from Scopus.
Volume 8, Issue 1, March 2010, Pages 77-80
Dapeng Wang | Dapeng Wang | Yubin Zhang | Yubin Zhang | Yubin Zhang | Zhang Zhang | Jiang Zhu | Jiang Zhu | Jun Yu | Jun Yu
We present an integrated stand-alone software package named KaKs_Calculator 2.0 as an updated version. It incorporates 17 methods for the calculation of nonsynonymous and synonymous substitution rates; among them, we added our modified versions of several widely used methods as the gamma series including γ-NG, γ-LWL, γ-MLWL, γ-LPB, γ-MLPB, γ-YN and γ-MYN, which have been demonstrated to perform better under certain conditions than their original forms and are not implemented in the previous version. The package is readily used for the identification of positively selected sites based on a sliding window across the sequences of interests in 5' to 3' direction of protein-coding sequences, and have improved the overall performance on sequence analysis for evolution studies. A toolbox, including C++ and Java source code and executable files on both Windows and Linux platforms together with a user instruction, is downloadable from the website for academic purpose at https://sourceforge.net/projects/kakscalculator2/. © 2010 Beijing Genomics Institute.
Volume 11, Issue 1, February 2013, Pages 8-17
Yamei Niu | Xu Zhao | Xu Zhao | Yong Sheng Wu | Ming Ming Li | Ming Ming Li | Xiu Jie Wang | Yun Gui Yang | Yun Gui Yang
N6-methyl-adenosine (m6A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m6A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3'-untranslated region (3'-UTR) as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m6A demethylation in an α-ketoglutarate (α-KG)- and Fe2+-dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from development and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role of m6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances. © 2013.
Volume 10, Issue 5, October 2012, Pages 239-245
Paul Graves | Yan Zeng
MicroRNAs (miRNAs) are approximately 22-nucleotide-long non-coding RNAs that are important regulators of gene expression in eukaryotes. miRNAs are first transcribed as long primary transcripts, which then undergo a series of processing steps to produce the single-stranded mature miRNAs. This article reviews our current knowledge of the mechanism and regulation of mammalian miRNA expression and points out areas of research that may enhance our understanding of how the specificity and efficiency of miRNA production is controlled in vivo. © 2012.
A Multifunctional Lentiviral-Based Gene Knockdown with Concurrent Rescue that Controls for Off-Target Effects of RNAi
Volume 8, Issue 4, December 2010, Pages 238-245
Yunfeng Feng | Linghu Nie | Meghna Das Thakur | Qin Su | Zhenfen Chi | Yongliang Zhao | Gregory D. Longmore
The efficient, stable delivery of siRNA into cells, and the appropriate controls for non-specific off-target effects of siRNA are major limitations to functional studies using siRNA technology. To overcome these drawbacks, we have developed a single lentiviral vector that can concurrently deplete endogenous gene expression while expressing an epitope-tagged siRNA-resistant target gene in the same cell. To demonstrate the functional utility of this system, we performed RNAi-depleted α-actinin-1 (α-ACTNl) expression in human T cells. α-ACTNl RNAi resulted in inhibited chemotaxis to SDF-lα, but it can be completely rescued by concurrent expression of RNAi-resistant α-ACTNl (rr-α-ACTNl) in the same cell. The presence of a GFP tag on rr-α-ACTNl allowed for detection of appropriate subcellular localization of rr-α-ACTNl. This system provides not only an internal control for RNAi off-target effects, but also the potential tool for rapid structure-function analyses and gene therapy. © 2010 Beijing Genomics Institute.
Volume 10, Issue 5, October 2012, Pages 295-301
Yu Li | Kris V. Kowdley
MicroRNAs (miRNAs) are a class of short non-coding RNA molecules that have attracted tremendous attention from the biological and biomedical research communities over the past decade. With over 1900 miRNAs discovered in humans to date, many of them have already been implicated in common human disorders. Facilitated by high-throughput genomics and bioinformatics in conjunction with traditional molecular biology techniques and animal models, miRNA research is now positioned to make the transition from laboratories to clinics to deliver profound benefits to public health. Herein, we overview the progress of miRNA research related to human diseases, as well as the potential for miRNA to becoming the next generation of diagnostics and therapeutics. © 2012.
Bacterial Phosphoproteomic Analysis Reveals the Correlation Between Protein Phosphorylation and Bacterial Pathogenicity
Volume 9, Issues 4-5, October 2011, Pages 119-127
Ruiguang Ge | Weiran Shan
Increasing evidence shows that protein phosphorylation on serine, threonine and tyrosine residues is a major regulatory post-translational modification in the bacteria. This review focuses on the implications of bacterial phosphoproteome in bacterial pathogenicity and highlights recent development of methods in phosphoproteomics and the connectivity of the phosphorylation networks. Recent technical developments in the high accuracy mass spectrometry have dramatically transformed proteomics and made it possible the characterization of a few exhaustive site-specific bacterial phosphoproteomes. The high abundance of tyrosine phosphorylations in a few bacterial phosphoproteomes suggests their roles in the pathogenicity, especially in the case of pathogen-host interactions; the high abundance of multi-phosphorylation sites in bacterial phosphoprotein is a compensation of the relatively small phosphorylation size and an indicator of the delicate regulation of protein functions. © 2011 Beijing Genomics Institute.
MicroRNA Regulation in Extreme Environments: Differential Expression of MicroRNAs in the Intertidal Snail Littorina littorea During Extended Periods of Freezing and Anoxia
Volume 10, Issue 5, October 2012, Pages 302-309
Kyle K. Biggar | Samantha F. Kornfeld | Yulia Maistrovski | Kenneth B. Storey
Several recent studies of vertebrate adaptation to environmental stress have suggested roles for microRNAs (miRNAs) in regulating global suppression of protein synthesis and/or restructuring protein expression patterns. The present study is the first to characterize stress-responsive alterations in the expression of miRNAs during natural freezing or anoxia exposures in an invertebrate species, the intertidal gastropod Littorina littorea. These snails are exposed to anoxia and freezing conditions as their environment constantly fluctuates on both a tidal and seasonal basis. The expression of selected miRNAs that are known to influence the cell cycle, cellular signaling pathways, carbohydrate metabolism and apoptosis was evaluated using RT-PCR. Compared to controls, significant changes in expression were observed for miR-1a-1, miR-34a and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-125b, miR-29b and miR-2a in foot muscle after freezing exposure at -6. °C for 24. h (P<0.05). In addition, in response to anoxia stress for 24. h, significant changes in expression were also observed for miR-1a-1, miR-210 and miR-29b in hepatopancreas and for miR-1a-1, miR-34a, miR-133a, miR-29b and miR-2a in foot muscle (P<0.05). Moreover, protein expression of Dicer, an enzyme responsible for mature microRNA processing, was increased in foot muscle during freezing and anoxia and in hepatopancreas during freezing. Alterations in expression of these miRNAs in L. littorea tissues may contribute to organismal survival under freezing and anoxia. © 2012.
Volume 11, Issue 3, June 2013, Pages 135-141
Hongzhu Qu | Xiangdong Fang
The ENCyclopedia Of DNA Elements (ENCODE) project is an international research consortium that aims to identify all functional elements in the human genome sequence. The second phase of the project comprised 1640 datasets from 147 different cell types, yielding a set of 30 publications across several journals. These data revealed that 80.4% of the human genome displays some functionality in at least one cell type. Many of these regulatory elements are physically associated with one another and further form a network or three-dimensional conformation to affect gene expression. These elements are also related to sequence variants associated with diseases or traits. All these findings provide us new insights into the organization and regulation of genes and genome, and serve as an expansive resource for understanding human health and disease. © 2013 .
Computational identification of miRNAs and their target genes from expressed sequence tags of tea (Camellia sinensis)
Volume 8, Issue 2, January 2010, Pages 113-121
G. R. Prabu | G. R. Prabu | A. K A Mandal | A. K A Mandal
MicroRNAs (miRNAs) are a newly identified class of small non-protein-coding post-transcriptional regulatory RNA in both plants and animals. The use of computational homology based search for expressed sequence tags (ESTs) with the Ambros empirical formula and other structural feature criteria filter is a suitable combination towards the discovery and isolation of conserved miRNAs from tea and other plant species whose genomes are not yet sequenced. In the present study, we blasted the database of tea (Camellia sinensis) ESTs to search for potential miRNAs, using previously known plant miRNAs. For the first time, four candidate miRNAs from four families were identified in tea. Using the newly identified miRNA sequences, a total of 30 potential target genes were identified for 11 miRNA families; 6 of these predicted target genes encode transcription factors (20%), 16 target genes appear to play roles in diverse physiological processes (53%) and 8 target genes have hypothetical or unknown functions (27%). These findings considerably broaden the scope of understanding the functions of miRNA in tea. © 2010 Beijing Genomics Institute.
Volume 10, Issue 4, August 2012, Pages 181-185
Leroy Hood | Qiang Tian
The development and application of systems strategies to biology and disease are transforming medical research and clinical practice in an unprecedented rate. In the foreseeable future, clinicians, medical researchers, and ultimately the consumers and patients will be increasingly equipped with a deluge of personal health information, e.g., whole genome sequences, molecular profiling of diseased tissues, and periodic multi-analyte blood testing of biomarker panels for disease and wellness. The convergence of these practices will enable accurate prediction of disease susceptibility and early diagnosis for actionable preventive schema and personalized treatment regimes tailored to each individual. It will also entail proactive participation from all major stakeholders in the health care system. We are at the dawn of predictive, preventive, personalized, and participatory (P4) medicine, the fully implementation of which requires marrying basic and clinical researches through advanced systems thinking and the employment of high-throughput technologies in genomics, proteomics, nanofluidics, single-cell analysis, and computation strategies in a highly-orchestrated discipline we termed translational systems medicine. © 2012.
Volume 9, Issue 6, December 2011, Pages 183-199
Praveen Guleria | Monika Mahajan | Jyoti Bhardwaj | Sudesh Kumar Yadav
Small RNAs (sRNAs) are 18-30 nt non-coding regulatory elements found in diverse organisms, which were initially identified as small double-stranded RNAs in Caenorhabditis elegans. With the development of new and improved technologies, sRNAs have also been identified and characterized in plant systems. Among them, micro RNAs (miRNAs) and small interfering RNAs (siRNAs) are found to be very important riboregulators in plants. Various types of sRNAs differ in their mode of biogenesis and in their function of gene regulation. sRNAs are involved in gene regulation at both transcriptional and post-transcriptional levels. They are known to regulate growth and development of plants. Furthermore, sRNAs especially plant miRNAs have been found to be involved in various stress responses, such as oxidative, mineral nutrient deficiency, dehydration, and even mechanical stimulus. Therefore, in the present review, we focus on the current understanding of biogenesis and regulatory mechanisms of plant sRNAs and their responses to various abiotic stresses. © 2011 Beijing Genomics Institute.
Volume 10, Issue 5, October 2012, Pages 254-263
Paula H. ReyesHerrera | Elisa Ficarra
Nearly two decades have passed since the publication of the first study reporting the discovery of microRNAs (miRNAs). The key role of miRNAs in post-transcriptional gene regulation led to the performance of an increasing number of studies focusing on origins, mechanisms of action and functionality of miRNAs. In order to associate each miRNA to a specific functionality it is essential to unveil the rules that govern miRNA action. Despite the fact that there has been significant improvement exposing structural characteristics of the miRNA-mRNA interaction, the entire physical mechanism is not yet fully understood. In this respect, the development of computational algorithms for miRNA target prediction becomes increasingly important. This manuscript summarizes the research done on miRNA target prediction. It describes the experimental data currently available and used in the field and presents three lines of computational approaches for target prediction. Finally, the authors put forward a number of considerations regarding current challenges and future directions. © 2012.
Volume 10, Issue 5, October 2012, Pages 285-294
Cord F. Stäehler | Andreas Keller | Andreas Keller | Petra Leidinger | Christina Backes | Anoop Chandran | Jöerg Wischhusen | Benjamin Meder | Eckart Meese
Co-regulation of genes has been extensively analyzed, however, rather limited knowledge is available on co-regulations within the miRNome. We investigated differential co-expression of microRNAs (miRNAs) based on miRNome profiles of whole blood from 540 individuals. These include patients suffering from different cancer and non-cancer diseases, and unaffected controls. Using hierarchical clustering, we found 9 significant clusters of co-expressed miRNAs containing 2-36 individual miRNAs. Through analyzing multiple sequencing alignments in the clusters, we found that co-expression of miRNAs is associated with both sequence similarity and genomic co-localization. We calculated correlations for all 371,953 pairs of miRNAs for all 540 individuals and identified 184 pairs of miRNAs with high correlation values. Out of these 184 pairs of miRNAs, 16 pairs (8.7%) were differentially co-expressed in unaffected controls, cancer patients and patients with non-cancer diseases. By computing correlated and anti-correlated miRNA pairs, we constructed a network with 184 putative co-regulations as edges and 100 miRNAs as nodes. Thereby, we detected specific clusters of miRNAs with high and low correlation values. Our approach represents the most comprehensive co-regulation analysis based on whole miRNome-wide expression profiling. Our findings further decrypt the interactions of miRNAs in normal and human pathological processes. © 2012.
Differential Expression of Mature MicroRNAs Involved in Muscle Maintenance of Hibernating Little Brown Bats, Myotis lucifugus: A Model of Muscle Atrophy Resistance
Volume 10, Issue 5, October 2012, Pages 295-301
Samantha F. Kornfeld | Kyle K. Biggar | Kenneth B. Storey
Muscle wasting is common in mammals during extended periods of immobility. However, many small hibernating mammals manage to avoid muscle atrophy despite remaining stationary for long periods during hibernation. Recent research has highlighted roles for short non-coding microRNAs (miRNAs) in the regulation of stress tolerance. We proposed that they could also play an important role in muscle maintenance during hibernation. To explore this possibility, a group of 10 miRNAs known to be normally expressed in skeletal muscle of non-hibernating mammals were analyzed by RT-PCR in hibernating little brown bats, Myotis lucifugus. We then compared the expression of these miRNAs in euthermic control bats and bats in torpor. Our results showed that compared to euthermic controls, significant, albeit modest (1.2-1.6 fold), increases in transcript expression were observed for eight mature miRNAs, including miR-1a-1, miR-29b, miR-181b, miR-15a, miR-20a, miR-206 and miR-128-1, in the pectoral muscle of torpid bats. Conversely, expression of miR-21 decreased by 80% during torpor, while expression of miR-107 remained unaffected. Interestingly, these miRNAs have been either validated or predicted to affect multiple muscle-specific factors, including myostatin, FoxO3a, HDAC4 and SMAD7, and are likely involved in the preservation of pectoral muscle mass and functionality during bat hibernation. © 2012.
Volume 10, Issue 1, February 2012, Pages 4-10
Peng Cui | Feng Ding | Qiang Lin | Lingfang Zhang | Ang Li | Zhang Zhang | Songnian Hu | Jun Yu
Here, we evaluate the contribution of two major biological processes-DNA replication and transcription-to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes. © 2012 Beijing Genomics Institute.
Study of Completed Archaeal Genomes and Proteomes: Hypothesis of Strong Mutational AT Pressure Existed in Their Common Predecessor
Volume 8, Issue 1, March 2010, Pages 22-32
Vladislav V. Khrustalev | Eugene V. Barkovsky
The number of completely sequenced archaeal genomes has been sufficient for a large-scale bioinformatic study. We have conducted analyses for each coding region from 36 archaeal genomes using the original CGS algorithm by calculating the total GC content (G+C), GC content in first, second and third codon positions as well as in fourfold and twofold degenerated sites from third codon positions, levels of arginine codon usage (Arg2: AGA/G; Arg4: CGX), levels of amino acid usage and the entropy of amino acid content distribution. In archaeal genomes with strong GC pressure, arginine is coded preferably by GC-rich Arg4 codons, whereas in most of archaeal genomes with G+C<0.6, arginine is coded preferably by AT-rich Arg2 codons. In the genome of Haloquadratum walsbyi, which is closely related to GC-rich archaea, GC content has decreased mostly in third codon positions, while Arg4>>Arg2 bias still persists. Proteomes of archaeal species carry characteristic amino acid biases: levels of isoleucine and lysine are elevated, while levels of alanine, histidine, glutamine and cytosine are relatively decreased. Numerous genomic and proteomic biases observed can be explained by the hypothesis of previously existed strong mutational AT pressure in the common predecessor of all archaea. © 2010 Beijing Genomics Institute.
Volume 9, Issues 1-2, April 2011, Pages 45-55
Sitanshu Sekhar Sahu | Ganapati Panda
Accurate identification of protein-coding regions (exons) in DNA sequences has been a challenging task in bioinformatics. Particularly the coding regions have a 3-base periodicity, which forms the basis of all exon identification methods. Many signal processing tools and techniques have been applied successfully for the identification task but still improvement in this direction is needed. In this paper, we have introduced a new promising model-independent time-frequency filtering technique based on S-transform for accurate identification of the coding regions. The S-transform is a powerful linear time-frequency representation useful for filtering in time-frequency domain. The potential of the proposed technique has been assessed through simulation study and the results obtained have been compared with the existing methods using standard datasets. The comparative study demonstrates that the proposed method outperforms its counterparts in identifying the coding regions. © 2011 Beijing Genomics Institute.
Volume 9, Issues 1-2, April 2011, Pages 7-14
Samanta Pino | Edward N. Trifonov | Edward N. Trifonov | Ernesto Di Mauro
In recent developments in chemistry and genetic engineering, the humble researcher dealing with the origin of life finds her(him)self in a grey area of tackling something that even does not yet have a clear definition agreed upon. A series of chemical steps is described to be considered as the life-nonlife transition, if one adheres to the minimalistic definition: life is self-reproduction with variations. The fully artificial RNA system chosen for the exploration corresponds sequence-wise to the reconstructed initial triplet repeats, presumably corresponding to the earliest protein-coding molecules. The demonstrated occurrence of the mismatches (variations) in otherwise complementary syntheses (" self-reproduction" ), in this RNA system, opens an experimental and conceptual perspective to explore the origin of life (and its definition), on the apparent edge of the origin. © 2011 Beijing Genomics Institute.
Volume 11, Issue 3, June 2013, Pages 158-165
Yajuan Li | Yajuan Li | Xiangdong Fang | Quan Zhen Li
Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), which is associated with significant morbidity and mortality of SLE patients. The pathogenesis of LN involves multiple factors, including genetic predisposition, epigenetic regulation and environmental interaction. Over the last decade, omics-based techniques have been extensively utilized for biomarker screening and a wide variety of variations which are associated with SLE and LN have been identified at the levels of genomics, transcriptomics and proteomics. These studies and discoveries have expanded our understanding of the molecular basis of the disease and are important for identification of potential therapeutic targets for disease prediction and early treatment. In this review, we summarize some of the recent studies targeted at the identification of LN-associated biomarkers using genomics and proteomic approaches. © 2013 .
CDS: A fold-change based statistical test for concomitant identification of distinctness and similarity in gene expression analysis
Volume 10, Issue 3, June 2012, Pages 127-135
Nicolas Tchitchek | José Felipe Golib Dzib | Brice Targat | Sebastian Noth | Arndt Benecke | Arndt Benecke | Annick Lesne | Annick Lesne
The problem of identifying differential activity such as in gene expression is a major defeat in biostatistics and bioinformatics. Equally important, however much less frequently studied, is the question of similar activity from one biological condition to another. The fold-change, or ratio, is usually considered a relevant criterion for stating difference and similarity between measurements. Importantly, no statistical method for concomitant evaluation of similarity and distinctness currently exists for biological applications. Modern microarray, digital PCR (dPCR), and Next-Generation Sequencing (NGS) technologies frequently provide a means of coefficient of variation estimation for individual measurements. Using fold-change, and by making the assumption that measurements are normally distributed with known variances, we designed a novel statistical test that allows us to detect concomitantly, thus using the same formalism, differentially and similarly expressed genes (http://cds.ihes.fr). Given two sets of gene measurements in different biological conditions, the probabilities of making type I and type II errors in stating that a gene is differentially or similarly expressed from one condition to the other can be calculated. Furthermore, a confidence interval for the fold-change can be delineated. Finally, we demonstrate that the assumption of normality can be relaxed to consider arbitrary distributions numerically. The Concomitant evaluation of Distinctness and Similarity (CDS) statistical test correctly estimates similarities and differences between measurements of gene expression. The implementation, being time and memory efficient, allows the use of the CDS test in high-throughput data analysis such as microarray, dPCR, and NGS experiments. Importantly, the CDS test can be applied to the comparison of single measurements (N=1) provided the variance (or coefficient of variation) of the signals is known, making CDS a valuable tool also in biomedical analysis where typically a single measurement per subject is available. © 2012.
Structure-based Comparative Analysis and Prediction of N-linked Glycosylation Sites in Evolutionarily Distant Eukaryotes
Volume 11, Issue 2, April 2013, Pages 96-104
Phuc Vinh Nguyen Lam | Phuc Vinh Nguyen Lam | Radoslav Goldman | Konstantinos Karagiannis | Tejas Narsule | Vahan Simonyan | Valerii Soika | Raja Mazumder
The asparagine-X-serine/threonine (NXS/T) motif, where X is any amino acid except proline, is the consensus motif for N-linked glycosylation. Significant numbers of high-resolution crystal structures of glycosylated proteins allow us to carry out structural analysis of the N-linked glycosylation sites (NGS). Our analysis shows that there is enough structural information from diverse glycoproteins to allow the development of rules which can be used to predict NGS. A Python-based tool was developed to investigate asparagines implicated in N-glycosylation in five species: Homo sapiens, Mus musculus, Drosophila melanogaster, Arabidopsis thaliana and Saccharomyces cerevisiae. Our analysis shows that 78% of all asparagines of NXS/T motif involved in N-glycosylation are localized in the loop/turn conformation in the human proteome. Similar distribution was revealed for all the other species examined. Comparative analysis of the occurrence of NXS/T motifs not known to be glycosylated and their reverse sequence (S/TXN) shows a similar distribution across the secondary structural elements, indicating that the NXS/T motif in itself is not biologically relevant. Based on our analysis, we have defined rules to determine NGS. Using machine learning methods based on these rules we can predict with 93% accuracy if a particular site will be glycosylated. If structural information is not available the tool uses structural prediction results resulting in 74% accuracy. The tool was used to identify glycosylation sites in 108 human proteins with structures and 2247 proteins without structures that have acquired NXS/T site/s due to non-synonymous variation. The tool, Structure Feature Analysis Tool (SFAT), is freely available to the public at http://hive.biochemistry.gwu.edu/tools/sfat. © 2013 .
Volume 8, Issue 2, January 2010, Pages 92-102
Kaifu Chen | Kaifu Chen | Lei Wang | Lei Wang | Meng Yang | Jiucheng Liu | Jiucheng Liu | Chengqi Xin | Chengqi Xin | Songnian Hu | Jun Yu
Our recent investigation in the protist Trichomonas vaginalis suggested a DNA sequence periodicity with a unit length of 120.9 nt, which represents a sequence signature for nucleosome positioning. We now extended our observation in higher eukaryotes and identified a similar periodicity of 175 nt in length in Caenorhabditis elegans. In the process of defining the sequence compositional characteristics, we found that the 10.5-nt periodicity, the sequence signature of DNA double helix, may not be sufficient for cross-nucleosome positioning but provides essential guiding rails to facilitate positioning. We further dissected nucleosome-protected sequences and identified a strong positive purine (AG) gradient from the 5'-end to the 3'-end, and also learnt that the nucleosome-enriched regions are GC-rich as compared to the nucleosome-free sequences as purine content is positively correlated with GC content. Sequence characterization allowed us to develop a hidden Markov model (HMM) algorithm for decoding nucleosome positioning computationally, and based on a set of training data from the fifth chromosome of C. elegans, our algorithm predicted 60%-70% of the well-positioned nucleosomes, which is 15%-20% higher than random positioning. We concluded that nucleosomes are not randomly positioned on DNA sequences and yet bind to different genome regions with variable stability, well-positioned nucleosomes leave sequence signatures on DNA, and statistical positioning of nucleosomes across genome can be decoded computationally based on these sequence signatures. © 2010 Beijing Genomics Institute.
Volume 8, Issue 1, March 2010, Pages 57-71
Guillaume Brysbaert | François Xavier Pellay | Sebastian Noth | Arndt Benecke
In view of potential application to biomedical diagnosis, tight transcriptome data quality control is compulsory. Usually, quality control is achieved using labeling and hybridization controls added at different stages throughout the processing of the biologic RNA samples. These control measures, however, only reflect the performance of the individual technical manipulations during the entire process and have no bearing as to the continued integrity of the RNA sample itself. Here we demonstrate that intrinsic statistical properties of the resulting transcriptome data signal and signal-variance distributions and their invariance can be identified independently of the animal species studied and the labeling protocol used. From these invariant properties we have developed a data model, the parameters of which can be estimated from individual experiments and used to compute relative quality measures based on similarity with large reference datasets. These quality measures add supplementary, non-redundant information to standard quality control estimates based on spike-in and hybridization controls, and are exploitable in data analysis. A software application for analyzing datasets as well as a reference dataset for AB1700 arrays are provided. They should allow AB1700 users to easily integrate this method into their analysis pipeline, and might instigate similar developments for other transcriptome platforms. © 2010 Beijing Genomics Institute.
Volume 8, Issue 1, March 2010, Pages 1-9
Lijun Zhang | Lijun Zhang | Xiaojun Zhang | Qing Ma | Honghao Zhou
Proteomics has been widely used in the last few years to look for new biomarkers and decipher the mechanism of HIV-host interaction. Herein, we review the recent developments of HIV/AIDS proteomic research, including the samples used in HIV/AIDS related research, the technologies used for proteomic study, the diagnosis biomarkers of HIV-associated disease especially HIV-associated neurocognitive impairment, the mechanisms of HIV-host interaction, HIV-associated dementia, substance abuse, and so on. In the end of this review, we also give some prospects about the limitation and future improvement of HIV/AIDS proteomic research. © 2010 Beijing Genomics Institute.
Volume 8, Issue 4, December 2010, Pages 262-267
Guanghong Zuo | Guanghong Zuo | Zhao Xu | Zhao Xu | Hongjie Yu | Hongjie Yu | Bailin Hao | Bailin Hao | Bailin Hao
Composition vector trees (CVTrees) are inferred from whole-genome data by an alignment-free and parameter-free method. The agreement of these trees with the corresponding taxonomy provides an objective justification of the inferred phylogeny In this work, we show the stability and self-consistency of CVTrees by performing bootstrap and jackknife re-sampling tests adapted to this alignment-free approach. Our ultimate goal is to advocate the viewpoint that time-consuming statistical re-sampling tests can be avoided at all in using this alignment-free approach. Agreement with taxonomy should be taken as a major criterion to estimate prokaryotic phylogenetic trees. © 2010 Beijing Genomics Institute.