Publications (19)47.36 Total impact
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Article: MeRIP-PF: An Easy-to-use Pipeline for High-resolution Peak-finding in MeRIP-Seq Data.
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ABSTRACT: RNA modifications, especially methylation of the N position of adenosine (A)-mA, represent an emerging research frontier in RNA biology. With the rapid development of high-throughput sequencing technology, in-depth study of mA distribution and function relevance becomes feasible. However, a robust method to effectively identify mA-modified regions has not been available yet. Here, we present a novel high-efficiency and user-friendly analysis pipeline called MeRIP-PF for the signal identification of MeRIP-Seq data in reference to controls. MeRIP-PF provides a statistical P-value for each identified mA region based on the difference of read distribution when compared to the controls and also calculates false discovery rate (FDR) as a cut off to differentiate reliable mA regions from the background. Furthermore, MeRIP-PF also achieves gene annotation of mA signals or peaks and produce outputs in both XLS and graphical format, which are useful for further study. MeRIP-PF is implemented in Perl and is freely available at http://software.big.ac.cn/MeRIP-PF.html.Genomics Proteomics & Bioinformatics 02/2013; 11(1):72-5. -
Article: An RNA-seq-based Gene Expression Profiling of Radiation-induced Tumorigenic Mammary Epithelial Cells.
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ABSTRACT: Immortality and tumorigenicity are two distinct characteristics of cancers. Immortalization has been suggested to precede tumorigenesis. To understand the molecular mechanisms of tumorigenicity and cancer progression in mammary epithelium, we established a tumorigenic cell model by means of heavy-ion radiation of an immortal cell model, which was created by overexpressing the human telomerase reverse transcriptase (hTERT) in normal human mammary epithelial cells. We examined the expression profile of this tumorigenic cell line (T_hMEC) using the hTERT-overexpressing immortal cell line (I_hMEC) as a control. In-depth RNA-seq data was generated by using the next-generation sequencing (NGS) platform (Life Technologies SOLiD3). We found that house-keeping (HK) and tissue-specific (TS) genes were differentially regulated during the tumorigenic process. HK genes tended to be activated while TS genes tended to be repressed. In addition, the HK genes and TS genes tended to contribute differentially to the variation of gene expression at different RPKM (gene expression in reads per exon kilobase per million mapped sequence reads) levels. Based on transcriptome analysis of the two cell lines, we defined 7053 differentially-expressed genes (DEGs) between immortality and tumorigenicity. Differential expression of 20 manually-selected genes was further validated using qRT-PCR. Our observations may help to further our understanding of cellular mechanism(s) in the transition from immortalization to tumorigenesis.Genomics Proteomics & Bioinformatics 12/2012; 10(6):326-35. -
Article: A comprehensive analysis of protein phosphatases in rice and Arabidopsis
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ABSTRACT: Protein phosphatases play essential roles in many cellular processes through the reversible protein phosphorylation that dictates many signal transduction pathways among organisms. Based on an in silico analysis, we classified 163 and 164 non-redundant protein phosphatases in rice and Arabidopsis, respectively. Protein serine/threonine phosphatases make up 67% of the total in both plants, in contrast to those of human, where this fraction is about 27%. Based on domain organization and intron composition analyses, we found that protein phosphatases in the two plants are highly conserved in structure. Evolutionary analysis suggests that segmental duplications occurring 40–70millionyears ago, contributed to the limited expansion of protein phosphatases. Gene expression analysis suggests that most phosphatases have broad expression spectra, with high abundance in four surveyed tissues (root, leaf, inflorescence, and seedling); only 46 and 12 phosphatases expressed in a single tissue of rice and Arabidopsis, respectively, regardless of their expression levels. Promoter analysis among different phosphatase subfamilies demonstrates a variable distribution of the w-box (a cis-element involved in disease resistance) between rice and Arabidopsis. KeywordsProtein phosphatases-Duplication-Expression-PromoterPlant Systematics and Evolution 04/2012; 289(3):111-126. · 1.34 Impact Factor -
Article: The association between H3K4me3 and antisense transcription.
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ABSTRACT: Histone H3 lysine 4 trimethylation (H3K4me3) is well known to occur in the promoter region of genes for transcription activation. However, when investigating the H3K4me3 profiles in the mouse cerebrum and testis, we discovered that H3K4me3 also has a significant enrichment at the 3' end of actively transcribed (sense) genes, named as 3'-H3K4me3. 3'-H3K4me3 is associated with ~15% of protein-coding genes in both tissues. In addition, we examined the transcriptional initiation signals including RNA polymerase II (RNAPII) binding sites and 5'-CAGE-tag that marks transcriptional start sites. Interestingly, we found that 3'-H3K4me3 is associated with the initiation of antisense transcription. Furthermore, 3'-H3K4me3 modification levels correlate positively with the antisense expression levels of the associated sense genes, implying that 3'-H3K4me3 is involved in the activation of antisense transcription. Taken together, our findings suggest that H3K4me3 may be involved in the regulation of antisense transcription that initiates from the 3' end of sense genes. In addition, a positive correlation was also observed between the expression of antisense and the associated sense genes with 3'-H3K4me3 modification. More importantly, we observed the 3'-H3K4me3 enrichment among genes in human, fruitfly and Arabidopsis, and found that the sequences of 3'-H3K4me3-marked regions are highly conserved and essentially indistinguishable from known promoters in vertebrate. Therefore, we speculate that these 3'-H3K4me3-marked regions may serve as potential promoters for antisense transcription and 3'-H3K4me3 appear to be a universal epigenetic feature in eukaryotes. Our results provide a novel insight into the epigenetic roles of H3K4me3 and the regulatory mechanism of antisense transcription.Genomics Proteomics & Bioinformatics 04/2012; 10(2):74-81. -
Article: Comparative analyses of H3K4 and H3K27 trimethylations between the mouse cerebrum and testis.
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ABSTRACT: The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. However, the bivalent domains tend towards a "winner-takes-all" approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a "winner-takes-all" principle to regulate gene expression.Genomics Proteomics & Bioinformatics 04/2012; 10(2):82-93. -
Article: Mechanism Analysis of Acid Tolerance Response of Bifidobacterium longum subsp. longum BBMN 68 by Gene Expression Profile Using RNA-Sequencing.
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ABSTRACT: To analyze the mechanism of the acid tolerance response (ATR) in Bifidobacterium longum subsp. longum BBMN68, we optimized the acid-adaptation condition to stimulate ATR effectively and analyzed the change of gene expression profile after acid-adaptation using high-throughput RNA-Seq. After acid-adaptation at pH 4.5 for 2 hours, the survival rate of BBMN68 at lethal pH 3.5 for 120 min was increased by 70 fold and the expression of 293 genes were upregulated by more than 2 fold, and 245 genes were downregulated by more than 2 fold. Gene expression profiling of ATR in BBMN68 suggested that, when the bacteria faced acid stress, the cells strengthened the integrity of cell wall and changed the permeability of membrane to keep the H(+) from entering. Once the H(+) entered the cytoplasm, the cells showed four main responses: First, the F(0)F(1)-ATPase system was initiated to discharge H(+). Second, the ability to produce NH(3) by cysteine-cystathionine-cycle was strengthened to neutralize excess H(+). Third, the cells started NER-UVR and NER-VSR systems to minimize the damage to DNA and upregulated HtpX, IbpA, and γ-glutamylcysteine production to protect proteins against damage. Fourth, the cells initiated global response signals ((p)ppGpp, polyP, and Sec-SRP) to bring the whole cell into a state of response to the stress. The cells also secreted the quorum sensing signal (AI-2) to communicate between intraspecies cells by the cellular signal system, such as two-component systems, to improve the overall survival rate. Besides, the cells varied the pathways of producing energy by shifting to BCAA metabolism and enhanced the ability to utilize sugar to supply sufficient energy for the operation of the mechanism mentioned above. Based on these reults, it was inferred that, during industrial applications, the acid resistance of bifidobacteria could be improved by adding BCAA, γ-glutamylcysteine, cysteine, and cystathionine into the acid-stress environment.PLoS ONE 01/2012; 7(12):e50777. · 4.09 Impact Factor -
Article: wapRNA: a web-based application for the processing of RNA sequences.
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ABSTRACT: mRNA/miRNA-seq technology is becoming the leading technology to globally profile gene expression and elucidate the transcriptional regulation mechanisms in living cells. Although there are many tools available for analyzing RNA-seq data, few of them are available as easy accessible online web tools for processing both mRNA and miRNA data for the RNA-seq based user community. As such, we have developed a comprehensive web application tool for processing mRNA-seq and miRNA-seq data. Our web tool wapRNA includes four different modules: mRNA-seq and miRNA-seq sequenced from SOLiD or Solexa platform and all the modules were tested on previously published experimental data. We accept raw sequence data with an optional reads filter, followed by mapping and gene annotation or miRNA prediction. wapRNA also integrates downstream functional analyses such as Gene Ontology, KEGG pathway, miRNA targets prediction and comparison of gene's or miRNA's different expression in different samples. Moreover, we provide the executable packages for installation on user's local server. wapRNA is freely available for use at http://waprna.big.ac.cn. The executable packages and the instruction for installation can be downloaded from our web site. husn@big.ac.cn; songshh@big.ac.cn. Supplementary data are available at Bioinformatics online.Bioinformatics 09/2011; 27(21):3076-7. · 5.47 Impact Factor -
Article: Complete genome sequence of the pathogenic bacterium Riemerella anatipestifer strain RA-GD.
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ABSTRACT: Riemerella anatipestifer is a well-described pathogen of waterfowl and other avian species which can cause a great loss to the poultry industry. Here we obtained the complete genome sequence of R. anatipestifer strain RA-GD, which was isolated from an infected duck in Guangzhou, China, and was cultivated in our laboratory.Journal of bacteriology 03/2011; 193(11):2896-7. · 3.94 Impact Factor -
Article: Complete genome sequence of Bifidobacterium longum subsp. longum BBMN68, a new strain from a healthy chinese centenarian.
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ABSTRACT: Bifidobacterium longum subsp. longum BBMN68 was isolated from the feces of a healthy centenarian living in an area of BaMa, Guangxi, China, known for longevity. Here we report the main genome features of B. longum strain BBMN68 and the identification of several predicted proteins associated with the ecological niche of longevity.Journal of bacteriology 02/2011; 193(3):787-8. · 3.94 Impact Factor -
Article: Thousands of Novel Transcripts Identified in Mouse Cerebrum, Testis, and ES Cells Based on ribo-minus RNA Sequencing.
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ABSTRACT: The high-throughput next-generation sequencing technologies provide an excellent opportunity for the detection of less-abundance transcripts that may not be identifiable by previously available techniques. Here, we report a discovery of thousands of novel transcripts (mostly non-coding RNAs) that are expressed in mouse cerebrum, testis, and embryonic stem (ES) cells, through an in-depth analysis of rmRNA-seq data. These transcripts show significant associations with transcriptional start and elongation signals. At the upstream of these transcripts we observed significant enrichment of histone marks (histone H3 lysine 4 trimethylation, H3K4me3), RNAPII binding sites, and cap analysis of gene expression tags that mark transcriptional start sites. Along the length of these transcripts, we also observed enrichment of histone H3 lysine 36 trimethylation (H3K36me3). Moreover, these transcripts show strong purifying selection in their genomic loci, exonic sequences, and promoter regions, implying functional constraints on the evolution of these transcripts. These results define a collection of novel transcripts in the mouse genome and indicate their potential functions in the mouse tissues and cells.Frontiers in genetics. 01/2011; 2:93. -
Article: Discovery, identification and comparative analysis of non-specific lipid transfer protein (nsLtp) family in Solanaceae.
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ABSTRACT: Plant non-specific lipid transfer proteins (nsLtps) have been reported to be involved in plant defense activity against bacterial and fungal pathogens. In this study, we identified 135 (122 putative and 13 previously identified) Solanaceae nsLtps, which are clustered into 8 different groups. By comparing with Boutrot's nsLtp classification, we classified these eight groups into five types (I, II, IV, IX and X). We compared Solanaceae nsLtps with Arabi-dopsis and Gramineae nsLtps and found that (1) Types I, II and IV are shared by Solanaceae, Gramineae and Arabidopsis; (2) Types III, V, VI and VIII are shared by Gramineae and Arabidopsis but not detected in Solanaceae so far; (3) Type VII is only found in Gramineae whereas type IX is present only in Arabidopsis and Solanaceae; (4) Type X is a new type that accounts for 52.59% Solanaceae nsLtps in our data, and has not been reported in any other plant so far. We further built and compared the three-dimensional structures of the eight groups, and found that the major functional diversification within the nsLtp family could be predated to the monocot/dicot divergence, and many gene duplications and sequence variations had happened in the nsLtp family after the monocot/dicot divergence, especially in Solanaceae.Genomics Proteomics & Bioinformatics 12/2010; 8(4):229-37. -
Article: Analysis and comparison of a set of expressed sequence tags of the parthenogenetic water flea Daphnia carinata.
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ABSTRACT: The water flea Daphnia carinata (D. carinata) reproduces both sexually and parthenogenetically, yet little is known about the genes involved in these processes. To further clarify the reproductive biology of Daphnia and elucidate their unique mechanism of reproductive transformation, we have generated and characterized an expressed sequence tag (EST) data set from D. carinata. A set of 1,495 clusters were generated from sequencing 3,072 randomly chosen clones from a parthenogenetic, juvenile water flea cDNA library. The nucleic acid and deduced amino acid sequences were compared with known GenBank sequences. Functional annotation found that 959 clusters showed significant homology with known genes involved in a broad range of activities, including metabolism, translation, development and reproduction, as well as genes involved in sensing environmental factors. We speculate that genes involved in development and reproduction, along with genes that allow the organism to sense changes in the environment, play important roles in the process of parthenogenetic reproduction and could be markers of the early steps of sexual differentiation. Additionally, 86% of the D. Carinata unique sequences could be stringently mapped to the D. pulex genome, of which 125 mapped to intergenic and intronic regions on the current assembly. Our results provide practical insight into crustacean reproductive biology, in addition to establishing a new animal model for reproductive and developmental biology.MGG Molecular & General Genetics 06/2009; 282(2):197-203. · 2.58 Impact Factor -
Article: Discovery of immune-related genes in Chinese mitten crab (Eriocheir sinensis) by expressed sequence tag analysis of haemocytes.
Aquaculture 01/2009; 287(3-4):297-303. · 2.04 Impact Factor -
Article: HRGD: a database for mining potential heterosis-related genes in plants.
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ABSTRACT: Heterosis-Related Gene Database (HRGD) is designed to manage the output of comparative transcriptomic studies related to heterosis (or hybrid vigor) among major agricultural crops, providing publicly available query and analysis platform for practical data mining. The database contains information concerning over 5,000 differentially expressed genes (DEGs) among the hybrid-parent tissue panels from rice genomes generated in our institute and other genomes of major cereal crops collected from published literatures. We have annotated relevant genes from manually extracted information includes not only gene sequences, genomic structures, and functional annotations but also empirical expression data generated based on various large-scale genomic methods. Tools for visualization and functional analysis of DEGs from various hybrid-parent tissue panels are also integrated via a user-friendly web interface. HRGD is a useful tool for helping plant biologists and crop breeders to explore biological knowledge that is being generated on a daily basis and in a large scale. The HRGD data resource is publicly available at http://hrgd.genomics.org.cn/ .Plant Molecular Biology 12/2008; 69(3):255-60. · 4.15 Impact Factor -
Article: Transcriptomic profiling of mature embryo from an elite super-hybrid rice LYP9 and its parental lines.
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ABSTRACT: The mature embryo of rice (Oryza sativa, L.) is a synchronized and integrated tissue mass laying the foundation at molecular level for its growth, development, and differentiation toward a developing and ultimately a mature plant. We carried out an EST (expressed-sequence-tags)-based transcriptomic study, aiming at gaining molecular insights into embryonic development of a rice hybrid triad-an elite hybrid rice LYP9 and its parental lines (93-11 and PA64s)-and possible relatedness to heterosis. We generated 27,566 high-quality ESTs from cDNA libraries made from mature rice embryos. We classified these ESTs into 7,557 unigenes (2,511 contigs and 5,046 singletons) and 7,250 (95.9%) of them were annotated. We noticed that the high-abundance genes in mature rice embryos belong to two major functional categories, stress-tolerance and preparation-for-development, and we also identified 191 differentially-expressed genes (General Chi-squared test, P-value <= 0.05) between LYP9 and its parental lines, representing typical expression patterns including over-dominance, high- and low-parent dominance, additivity, and under-dominance. In LYP9, the majority of embryo-associated genes were found not only abundantly and specifically enriched but also significantly up-regulated. Our results suggested that massively strengthening tissue-(or stage-) characteristic functions may contribute to heterosis rather than a few simple mechanistic explanations at the individual gene level. In addition, the large collection of rice embryonic ESTs provides significant amount of data for future comparative analyses on plant development, especially for the important crops of the grass family.BMC Plant Biology 11/2008; 8:114. · 3.45 Impact Factor -
Article: Proteomic profiling of rice embryos from a hybrid rice cultivar and its parental lines.
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ABSTRACT: Elite rice hybrids, when compared to their parental lines, exhibit increased yield and other favorable agronomical traits, such as pathogen- and water-stress resistances, which are described as heterosis, and the molecular mechanism of heterosis remains to be elucidated. Since genomic sequences of the paternal (9311) and maternal lines (P64S) of a major rice hybrid variety LYP9 (Liang-You-Pei-Jiu) were acquired recently, we performed a proteomic study on mature embryos of this hybrid triad based on 2-DE and MALDI-TOF MS analyses, and identified 54 differentially expressed proteins involved in major biological processes including nutrient reservoir, response to stress, and metabolism. We observed that most of the storage proteins exhibit overdominance and stress-induced proteins display additivity. We compared proteomic results with transcriptomic data generated from the same embryo samples and found 28 candidate heterosis-associated genes shared by the two datasets. We further traced back to their genomic structures including protein-coding and regulatory regions and found that most of these genes have multiple copies in rice genomes as paralogous genes. Based on alignment of coding and regulation regions, we found that most of the differentially expressed genes at both protein and RNA levels are recent gene duplicates (paralogous genes) with relative little difference in protein-coding regions between orthologous genes (between genes of the two parental genomes) as compared to regulatory regions that harbor numerous indels and base substitutions.Proteomics 11/2008; 8(22):4808-21. · 4.43 Impact Factor -
Article: Proteomic profiling of rice embryos from a hybrid rice cultivar and its parental lines
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ABSTRACT: Elite rice hybrids, when compared to their parental lines, exhibit increased yield and other favorable agronomical traits, such as pathogen- and water-stress resistances, which are described as heterosis, and the molecular mechanism of heterosis remains to be elucidated. Since genomic sequences of the paternal (9311) and maternal lines (P64S) of a major rice hybrid variety LYP9 (Liang-You-Pei-Jiu) were acquired recently, we performed a proteomic study on mature embryos of this hybrid triad based on 2-DE and MALDI-TOF MS analyses, and identified 54 differentially expressed proteins involved in major biological processes including nutrient reservoir, response to stress, and metabolism. We observed that most of the storage proteins exhibit overdominance and stress-induced proteins display additivity. We compared proteomic results with transcriptomic data generated from the same embryo samples and found 28 candidate heterosis-associated genes shared by the two datasets. We further traced back to their genomic structures including protein-coding and regulatory regions and found that most of these genes have multiple copies in rice genomes as paralogous genes. Based on alignment of coding and regulation regions, we found that most of the differentially expressed genes at both protein and RNA levels are recent gene duplicates (paralogous genes) with relative little difference in protein-coding regions between orthologous genes (between genes of the two parental genomes) as compared to regulatory regions that harbor numerous indels and base substitutions.Proteomics 10/2008; 8(22):4808 - 4821. · 4.43 Impact Factor -
Article: How many human genes can be defined as housekeeping with current expression data?
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ABSTRACT: Housekeeping (HK) genes are ubiquitously expressed in all tissue/cell types and constitute a basal transcriptome for the maintenance of basic cellular functions. Partitioning transcriptomes into HK and tissue-specific (TS) genes relatively is fundamental for studying gene expression and cellular differentiation. Although many studies have aimed at large-scale and thorough categorization of human HK genes, a meaningful consensus has yet to be reached. We collected two latest gene expression datasets (both EST and microarray data) from public databases and analyzed the gene expression profiles in 18 human tissues that have been well-documented by both two data types. Benchmarked by a manually-curated HK gene collection (HK408), we demonstrated that present data from EST sampling was far from saturated, and the inadequacy has limited the gene detectability and our understanding of TS expressions. Due to a likely over-stringent threshold, microarray data showed higher false negative rate compared with EST data, leading to a significant underestimation of HK genes. Based on EST data, we found that 40.0% of the currently annotated human genes were universally expressed in at least 16 of 18 tissues, as compared to only 5.1% specifically expressed in a single tissue. Our current EST-based estimate on human HK genes ranged from 3,140 to 6,909 in number, a ten-fold increase in comparison with previous microarray-based estimates. We concluded that a significant fraction of human genes, at least in the currently annotated data depositories, was broadly expressed. Our understanding of tissue-specific expression was still preliminary and required much more large-scale and high-quality transcriptomic data in future studies. The new HK gene list categorized in this study will be useful for genome-wide analyses on structural and functional features of HK genes.BMC Genomics 02/2008; 9:172. · 4.07 Impact Factor -
Article: Differential gene expression in an elite hybrid rice cultivar (Oryza sativa, L) and its parental lines based on SAGE data.
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ABSTRACT: It was proposed that differentially-expressed genes, aside from genetic variations affecting protein processing and functioning, between hybrid and its parents provide essential candidates for studying heterosis or hybrid vigor. Based our serial analysis of gene expression (SAGE) data from an elite Chinese super-hybrid rice (LYP9) and its parental cultivars (93-11 and PA64s) in three major tissue types (leaves, roots and panicles) at different developmental stages, we analyzed the transcriptome and looked for candidate genes related to rice heterosis. By using an improved strategy of tag-to-gene mapping and two recently annotated genome assemblies (93-11 and PA64s), we identified 10,268 additional high-quality tags, reaching a grand total of 20,595 together with our previous result. We further detected 8.5% and 5.9% physically-mapped genes that are differentially-expressed among the triad (in at least one of the three stages) with P-values less than 0.05 and 0.01, respectively. These genes distributed in 12 major gene expression patterns; among them, 406 up-regulated and 469 down-regulated genes (P < 0.05) were observed. Functional annotations on the identified genes highlighted the conclusion that up-regulated genes (some of them are known enzymes) in hybrid are mostly related to enhancing carbon assimilation in leaves and roots. In addition, we detected a group of up-regulated genes related to male sterility and 442 down-regulated genes related to signal transduction and protein processing, which may be responsible for rice heterosis. We improved tag-to-gene mapping strategy by combining information from transcript sequences and rice genome annotation, and obtained a more comprehensive view on genes that related to rice heterosis. The candidates for heterosis-related genes among different genotypes provided new avenue for exploring the molecular mechanism underlying heterosis.BMC Plant Biology 01/2007; 7:49. · 3.45 Impact Factor
Top co-authors
Top Journals
Institutions
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2007–2013
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Beijing Genomics Institute
Shenzhen, Guangdong Sheng, China
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2012
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Zhejiang University
Hangzhou, Zhejiang Sheng, China
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