近年来,基于单分子测序技术的ISO-seq数据以其超长读段长度被越来越多地应用于转录组新型异构体预测研究,但目前大多数研究工作只用到全长读段数据,丢失了非全长读段数据中较多有用信息,因而数据没有得到充分利用。针对这一问题,本文在...近年来,基于单分子测序技术的ISO-seq数据以其超长读段长度被越来越多地应用于转录组新型异构体预测研究,但目前大多数研究工作只用到全长读段数据,丢失了非全长读段数据中较多有用信息,因而数据没有得到充分利用。针对这一问题,本文在保留非全长读段的基础上提出了两个能同时预测异构体结构和计算其表达比例的模型基于狄利克雷采样的异构体探测与预测(Dirichletsampling for isoform detection and prediction,DSIDP)和基于马尔科夫链的异构体探测与预测(Markovchain for isoform detection and predition,MCIDP)。两个模型均从全长读段中建立异构体预测集,并采用全长读段和非全长读段计算异构体表达比例。DSIDP将所有读段比对至异构体预测集,并使用Dirichlet采样解决多源映射问题,MCIDP使用马尔科夫链模拟基因外显子之间的选择性剪切,该模型还能预测出数据中没有全长读段的异构体。本文采用模拟数据和真实数据验证了两个模型的有效性。展开更多
基于高通量测序的RNA-Seq(RNA-sequencing)是用于转录组研究的一种新技术,针对该技术在转录组表达分析研究中存在的读段多源映射和读段非均匀分布等难点,提出一个改进的转录组表达研究方法 LDASeqII(Improvement of latent Dirichlet al...基于高通量测序的RNA-Seq(RNA-sequencing)是用于转录组研究的一种新技术,针对该技术在转录组表达分析研究中存在的读段多源映射和读段非均匀分布等难点,提出一个改进的转录组表达研究方法 LDASeqII(Improvement of latent Dirichlet allocation for sequencing data)。模型利用剪接异构体结构信息对参数进行约束并进行外显子读段数目归一化处理,解决了读段非均匀分布下的多源映射问题。通过引入"伪外显子"和"伪转录本"分别处理接合区读段和噪声读段。将模型应用到真实数据集上,并与原LDASeq(Latent Dirichlet allocation for sequencing data)模型和目前流行的Cufflinks与RSEM(RNA-Seq by expectation maximization)方法进行对比。结果显示,改进方法获得了更为准确的转录本及基因表达水平计算结果。展开更多
Objective: To construct recombinant retroviral vector containing HIV-1 Tatgene and evaluate the junction of the expressed Tat in target cells. Methods: HIV-1 Tat_(101) genewas recovered from pEV plasmid by Hind Ⅲ dig...Objective: To construct recombinant retroviral vector containing HIV-1 Tatgene and evaluate the junction of the expressed Tat in target cells. Methods: HIV-1 Tat_(101) genewas recovered from pEV plasmid by Hind Ⅲ digestion and cloned into expression plasmid LZESpBMN-Z toconstruct recombinant retroviral expression plasmid named LZRS-Tat_(101). Using the method ofcalcium phosphate, the construct of LZRS-Tat_(101) was then transfected into packaging cell linesPhoenix (ΦNX) which contained env and gal genes encoding structural proteins and pol gene codingfor 3 enzymes ( reverse transcriptase, protease and integrate) essential for retroviral integrationand replication . The stable transfected cell lines was obtained using puromycin to screen for morethan 3 days. Then, immunohistochemical (IHC ) staining was carried out to detect the expressionlevel of Tat_(101) protein in both transiently and stably trancfected ΦNX, respectively. Thesupematants containing recombinant virus collected from transient and stable transfected cells wereemployed to infect 293 cells, respectively, and the expressed Tat in 293 cells was tested by Westernblot. Meantime, the supematants of infected 293 cells was further added to HL3T1 cells which wereHela cell lines containing an HIV-1-LTR/CAT reporter construct to establish a co-culture system.After co-culture for 72 hours, the protein was extracted from HL3T1 cells and used for CAT activityassay. Results: After LZRS- Tat_(101) was transfected into ΦNX, the amount of expressed Tat intransient transfection cells was significantly higher than that in stable transfection cells; Tatcould be detected not only in 293 cells but also in the supematants from 293 cells culture, and Tatin the supematants could activate HIV-1 LTR promoter in HL3T1, resulting in high 'expression of CATlocated at the downstream of LTR. Conclusion: The construct of recombinant retrovirus LZRS-Tat_(101) could express Tat protein in target cells and the expressed Tat was functionally activeand can really exhibit the ability to activate transcription.展开更多
Sea cucumber(Apostichopus japonicus) is one of the most important aquaculture animals in China. Usually its normal body color is black that fits its living environment. The juvenile individuals obtained by crossing al...Sea cucumber(Apostichopus japonicus) is one of the most important aquaculture animals in China. Usually its normal body color is black that fits its living environment. The juvenile individuals obtained by crossing albino sea cucumber segregated in body color. To document the transcriptome difference between albino associating sea cucumber and the control, we sequenced their transcriptomes with RNA-seq. Approximately, 4.790 million(M) and 4.884 M reads, 200 nt in length, were generated from the body wall of albino associating sea cucumber and the control, respectively, from them, 9550(46.81%) putative genes were identified. In total, 583 genes were found to express differentially between albino associating sea cucumber and the control. Of these differentially expressed genes(DEGs), 4.8% changed more than five-folds. The expression levels of eight DEGs were confirmed with real-time PCR. The changing trend of these DEGs detected with real-time PCR agreed well with that detected with RNA-seq, although the change degree of some DEGs was different. Four significantly enriched pathways were identified for DEGs, which included phagocytosis, Staphylococcus aureus infection, ECM-receptor interaction and focal adhesion. These pathways were helpful for understanding the physiological difference between albino associating sea cucumber and the control.展开更多
Through the widespread implementation of next-generation sequencing (NGS), analyses of the whole genome (the entire DNA content) and the whole transcriptome (the genes being expressed) are becoming commonplace. ...Through the widespread implementation of next-generation sequencing (NGS), analyses of the whole genome (the entire DNA content) and the whole transcriptome (the genes being expressed) are becoming commonplace. NGS enables the analysis of a vast amount of previously unattainable genetic information. Despite this potential, NGS has yet to be widely imple- mented in genetic studies of biological invasions. The study of the genomic causes and consequences of biological invasions al- lows a deeper understanding of the molecular mechanisms underpinning the invasion process. In this review, we present a brief introduction to NGS followed by a synthesis of current research in the genomics and transcriptomics of adaptation and coloniza- tion. We then highlight research opportunities in the field, including: (1) assembling genomes and transcriptomes of non-model organisms, (2) identifying genomic regions and candidate genes underlying evolutionary processes, and (3) studying the adaptive role of gene expression variation. In particular, because introduced species face a broad range of physiological and biotic chal- lenges when colonizing novel and variable environments, transcriptomics will enable the study of gene regulatory pathways that may be responsible for acclimation or adaptation. To conclude, we identify a number of research approaches that will aid our fu- ture understanding of biological invasions展开更多
De novo transcriptome assembly is an important approach in RNA-Seq data analysis and it can help us to reconstruct the transcriptome and investigate gene expression profiles without reference genome sequences.We carri...De novo transcriptome assembly is an important approach in RNA-Seq data analysis and it can help us to reconstruct the transcriptome and investigate gene expression profiles without reference genome sequences.We carried out transcriptome assemblies with two RNA-Seq datasets generated from human brain and cell line,respectively.We then determined an efficient way to yield an optimal overall assembly using three different strategies.We first assembled brain and cell line transcriptome using a single k-mer length.Next we tested a range of values of k-mer length and coverage cutoff in assembling.Lastly,we combined the assembled contigs from a range of k values to generate a final assembly.By comparing these assembly results,we found that using only one k-mer value for assembly is not enough to generate good assembly results,but combining the contigs from different k-mer values could yield longer contigs and greatly improve the overall assembly.展开更多
Long noncoding RNAs (lncRNAs) play important roles in various biological regulatory processes in yeast, mammals, and plants. However, no systematic identification of lncRNAs has been reported in Gossypium arboreum. ...Long noncoding RNAs (lncRNAs) play important roles in various biological regulatory processes in yeast, mammals, and plants. However, no systematic identification of lncRNAs has been reported in Gossypium arboreum. In this study, the strand-specific RNA sequencing (ssRNA-seq) of samples from cotton fibers and leaves was performed, and lncRNAs involved in fiber initiation and elongation processes were systematically identified and analyzed. We identified 5,996 lncRNAs, of which 3,510 and 2,486 can be classified as long intergenic noncoding RNAs (lincRNAs) and natural antisense transcripts (IncNAT), respectively. LincRNAs and lncNATs are similar in many aspects, but have some differences in exon number, exon length, and transcript length. Expression analysis revealed that 51.9% of lincRNAs and 54.5% of lncNATs transcripts were preferentially expressed at one stage of fiber development, and were significantly highly expressed than protein-coding tran- scripts (21.7%). During the fiber and rapid elongation stages, rapid and dynamic changes in lncRNAs may contribute to fiber development in cotton. This work describes a set of lncRNAs that are involved in fiber development. The characterization and expression analysis of lncRNAs will facilitate future studies on their roles in fiber development in cotton.展开更多
The lichen-forming fungus was isolated from the desert lichen Endocarpon pusillum that is extremely drought resistant.To understand the molecular mechanisms of drought resistance in the fungus,we employed RNA-seq and ...The lichen-forming fungus was isolated from the desert lichen Endocarpon pusillum that is extremely drought resistant.To understand the molecular mechanisms of drought resistance in the fungus,we employed RNA-seq and quantitative real-time PCR to compare and characterize the differentially expressed genes in pure culture at two different water levels and with that in desiccated lichen.The comparative transcriptome analysis indicated that a total of 1781 genes were differentially expressed between samples cultured under normal and PEG-induced drought stress conditions.Similar to those in drought resistance plants and non-lichenized fungi,the common drought-resistant mechanisms were differentially expressed in E.pusillum.However,the expression change of genes involved in osmotic regulation in E.pusillum is different,which might be the evidence for the feature of drought adaptation.Interestingly,different from other organisms,some genes involved in drought adaption mechanisms showed significantly different expression patterns between the presence and absence of drought stress in E.pusillum.The expression of 23 candidate stress responsive genes was further confirmed by quantitative real-time PCR using dehydrated E.pusillum lichen thalli.This study provides a valuable resource for future research on lichen-forming fungi and shall facilitate future functional studies of the specific genes related to drought resistance.展开更多
Panax ginseng C. A. Meyer is an important traditional herb in eastern Asia. It contains ginsenosides, which are primary bioactive compounds with medicinal properties. Although ginseng has been cultivated since at leas...Panax ginseng C. A. Meyer is an important traditional herb in eastern Asia. It contains ginsenosides, which are primary bioactive compounds with medicinal properties. Although ginseng has been cultivated since at least the Ming dynasty to increase production, cultivated ginseng has lower quantities of ginsenosides and lower disease resistance than ginseng grown under natural conditions. We extracted root RNA from six varieties of fifth-year P. ginseng cultivars representing four different growth conditions, and performed Illumina paired-end sequencing. In total, 163,165,706 raw reads were obtained and used to generate a de novo transcriptome that consisted of 151,763 contigs(76,336 unigenes), of which 100,648 contigs(66.3%) were successfully annotated. Differential expression analysis revealed that most differentially expressed genes(DEGs) were upregulated(246 out of 258, 95.3%) in ginseng grown under natural conditions compared with that grown under artificial conditions. These DEGs were enriched in gene ontology(GO) terms including response to stimuli and localization. In particular, some key ginsenoside biosynthesis-related genes, including HMG-Co A synthase(HMGS), mevalonate kinase(MVK), and squalene epoxidase(SE), were upregulated in wild-grown ginseng. Moreover, a high proportion of disease resistance-related genes were upregulated in wild-grown ginseng. This study is the first transcriptome analysis to compare wild-grown and cultivated ginseng, and identifies genes that may produce higher ginsenoside content and better disease resistance in the wild; these genes may have the potential to improve cultivated ginseng grown in artificial environments.展开更多
Research has shown that the hypomagnetic field(HMF)can affect embryo development,cell proliferation,learning and memory,and in vitro tubulin assembly.In the present study,we aimed to elucidate the molecular mechanism ...Research has shown that the hypomagnetic field(HMF)can affect embryo development,cell proliferation,learning and memory,and in vitro tubulin assembly.In the present study,we aimed to elucidate the molecular mechanism by which the HMF exerts its effect,by comparing the transcriptome profiles of human neuroblastoma cells exposed to either the HMF or the geomagnetic field.A total of 2464 differentially expressed genes(DEGs)were identified,216 of which were up-regulated and2248 of which were down-regulated after exposure to the HMF.These DEGs were found to be significantly clustered into several key processes,namely macromolecule localization,protein transport,RNA processing,and brain function.Seventeen DEGs were verified by real-time quantitative PCR,and the expression levels of nine of these DEGs were measured every 6 h.Most notably,MAPK1 and CRY2,showed significant up-and down-regulation,respectively,during the first 6 h of HMF exposure,which suggests involvement of the MAPK pathway and cryptochrome in the early bio-HMF response.Our results provide insights into the molecular mechanisms underlying the observed biological effects of the HMF.展开更多
文摘近年来,基于单分子测序技术的ISO-seq数据以其超长读段长度被越来越多地应用于转录组新型异构体预测研究,但目前大多数研究工作只用到全长读段数据,丢失了非全长读段数据中较多有用信息,因而数据没有得到充分利用。针对这一问题,本文在保留非全长读段的基础上提出了两个能同时预测异构体结构和计算其表达比例的模型基于狄利克雷采样的异构体探测与预测(Dirichletsampling for isoform detection and prediction,DSIDP)和基于马尔科夫链的异构体探测与预测(Markovchain for isoform detection and predition,MCIDP)。两个模型均从全长读段中建立异构体预测集,并采用全长读段和非全长读段计算异构体表达比例。DSIDP将所有读段比对至异构体预测集,并使用Dirichlet采样解决多源映射问题,MCIDP使用马尔科夫链模拟基因外显子之间的选择性剪切,该模型还能预测出数据中没有全长读段的异构体。本文采用模拟数据和真实数据验证了两个模型的有效性。
文摘基于高通量测序的RNA-Seq(RNA-sequencing)是用于转录组研究的一种新技术,针对该技术在转录组表达分析研究中存在的读段多源映射和读段非均匀分布等难点,提出一个改进的转录组表达研究方法 LDASeqII(Improvement of latent Dirichlet allocation for sequencing data)。模型利用剪接异构体结构信息对参数进行约束并进行外显子读段数目归一化处理,解决了读段非均匀分布下的多源映射问题。通过引入"伪外显子"和"伪转录本"分别处理接合区读段和噪声读段。将模型应用到真实数据集上,并与原LDASeq(Latent Dirichlet allocation for sequencing data)模型和目前流行的Cufflinks与RSEM(RNA-Seq by expectation maximization)方法进行对比。结果显示,改进方法获得了更为准确的转录本及基因表达水平计算结果。
基金National Natural Science Foundation of China(30100160,30271179)
文摘Objective: To construct recombinant retroviral vector containing HIV-1 Tatgene and evaluate the junction of the expressed Tat in target cells. Methods: HIV-1 Tat_(101) genewas recovered from pEV plasmid by Hind Ⅲ digestion and cloned into expression plasmid LZESpBMN-Z toconstruct recombinant retroviral expression plasmid named LZRS-Tat_(101). Using the method ofcalcium phosphate, the construct of LZRS-Tat_(101) was then transfected into packaging cell linesPhoenix (ΦNX) which contained env and gal genes encoding structural proteins and pol gene codingfor 3 enzymes ( reverse transcriptase, protease and integrate) essential for retroviral integrationand replication . The stable transfected cell lines was obtained using puromycin to screen for morethan 3 days. Then, immunohistochemical (IHC ) staining was carried out to detect the expressionlevel of Tat_(101) protein in both transiently and stably trancfected ΦNX, respectively. Thesupematants containing recombinant virus collected from transient and stable transfected cells wereemployed to infect 293 cells, respectively, and the expressed Tat in 293 cells was tested by Westernblot. Meantime, the supematants of infected 293 cells was further added to HL3T1 cells which wereHela cell lines containing an HIV-1-LTR/CAT reporter construct to establish a co-culture system.After co-culture for 72 hours, the protein was extracted from HL3T1 cells and used for CAT activityassay. Results: After LZRS- Tat_(101) was transfected into ΦNX, the amount of expressed Tat intransient transfection cells was significantly higher than that in stable transfection cells; Tatcould be detected not only in 293 cells but also in the supematants from 293 cells culture, and Tatin the supematants could activate HIV-1 LTR promoter in HL3T1, resulting in high 'expression of CATlocated at the downstream of LTR. Conclusion: The construct of recombinant retrovirus LZRS-Tat_(101) could express Tat protein in target cells and the expressed Tat was functionally activeand can really exhibit the ability to activate transcription.
基金funded by the National Natural Science Foundation of China (No. 40976089)the National Key Technology Support Program of China (No. 2011BAD13B02)+1 种基金the National Oceanic Public Welfare Industry Special Scientific Research of China (No. 201205023)the Chinese National 863 Project (2012AA10A412)
文摘Sea cucumber(Apostichopus japonicus) is one of the most important aquaculture animals in China. Usually its normal body color is black that fits its living environment. The juvenile individuals obtained by crossing albino sea cucumber segregated in body color. To document the transcriptome difference between albino associating sea cucumber and the control, we sequenced their transcriptomes with RNA-seq. Approximately, 4.790 million(M) and 4.884 M reads, 200 nt in length, were generated from the body wall of albino associating sea cucumber and the control, respectively, from them, 9550(46.81%) putative genes were identified. In total, 583 genes were found to express differentially between albino associating sea cucumber and the control. Of these differentially expressed genes(DEGs), 4.8% changed more than five-folds. The expression levels of eight DEGs were confirmed with real-time PCR. The changing trend of these DEGs detected with real-time PCR agreed well with that detected with RNA-seq, although the change degree of some DEGs was different. Four significantly enriched pathways were identified for DEGs, which included phagocytosis, Staphylococcus aureus infection, ECM-receptor interaction and focal adhesion. These pathways were helpful for understanding the physiological difference between albino associating sea cucumber and the control.
文摘Through the widespread implementation of next-generation sequencing (NGS), analyses of the whole genome (the entire DNA content) and the whole transcriptome (the genes being expressed) are becoming commonplace. NGS enables the analysis of a vast amount of previously unattainable genetic information. Despite this potential, NGS has yet to be widely imple- mented in genetic studies of biological invasions. The study of the genomic causes and consequences of biological invasions al- lows a deeper understanding of the molecular mechanisms underpinning the invasion process. In this review, we present a brief introduction to NGS followed by a synthesis of current research in the genomics and transcriptomics of adaptation and coloniza- tion. We then highlight research opportunities in the field, including: (1) assembling genomes and transcriptomes of non-model organisms, (2) identifying genomic regions and candidate genes underlying evolutionary processes, and (3) studying the adaptive role of gene expression variation. In particular, because introduced species face a broad range of physiological and biotic chal- lenges when colonizing novel and variable environments, transcriptomics will enable the study of gene regulatory pathways that may be responsible for acclimation or adaptation. To conclude, we identify a number of research approaches that will aid our fu- ture understanding of biological invasions
基金supported by the National Basic Research Program of China (Grant Nos. 2010CB945401, 2007CB108800)National Natural Science Foundation of China (Grant Nos. 30870575, 31071162,31000590)the Science and Technology Commission of Shanghai Municipality (Grant No. 11DZ2260300)
文摘De novo transcriptome assembly is an important approach in RNA-Seq data analysis and it can help us to reconstruct the transcriptome and investigate gene expression profiles without reference genome sequences.We carried out transcriptome assemblies with two RNA-Seq datasets generated from human brain and cell line,respectively.We then determined an efficient way to yield an optimal overall assembly using three different strategies.We first assembled brain and cell line transcriptome using a single k-mer length.Next we tested a range of values of k-mer length and coverage cutoff in assembling.Lastly,we combined the assembled contigs from a range of k values to generate a final assembly.By comparing these assembly results,we found that using only one k-mer value for assembly is not enough to generate good assembly results,but combining the contigs from different k-mer values could yield longer contigs and greatly improve the overall assembly.
基金the National Natural Science Foundation of China (31301369, 31271768, 31401425)
文摘Long noncoding RNAs (lncRNAs) play important roles in various biological regulatory processes in yeast, mammals, and plants. However, no systematic identification of lncRNAs has been reported in Gossypium arboreum. In this study, the strand-specific RNA sequencing (ssRNA-seq) of samples from cotton fibers and leaves was performed, and lncRNAs involved in fiber initiation and elongation processes were systematically identified and analyzed. We identified 5,996 lncRNAs, of which 3,510 and 2,486 can be classified as long intergenic noncoding RNAs (lincRNAs) and natural antisense transcripts (IncNAT), respectively. LincRNAs and lncNATs are similar in many aspects, but have some differences in exon number, exon length, and transcript length. Expression analysis revealed that 51.9% of lincRNAs and 54.5% of lncNATs transcripts were preferentially expressed at one stage of fiber development, and were significantly highly expressed than protein-coding tran- scripts (21.7%). During the fiber and rapid elongation stages, rapid and dynamic changes in lncRNAs may contribute to fiber development in cotton. This work describes a set of lncRNAs that are involved in fiber development. The characterization and expression analysis of lncRNAs will facilitate future studies on their roles in fiber development in cotton.
基金supported by the National Natural Science Foundation of China(31270018)the Knowledge Innovation Program of the Chinese Academy of Sciences(KSCX2-EW-J-6)the State Key Laboratory of Crop Stress Biology for Arid Areas,Northwest A&F University
文摘The lichen-forming fungus was isolated from the desert lichen Endocarpon pusillum that is extremely drought resistant.To understand the molecular mechanisms of drought resistance in the fungus,we employed RNA-seq and quantitative real-time PCR to compare and characterize the differentially expressed genes in pure culture at two different water levels and with that in desiccated lichen.The comparative transcriptome analysis indicated that a total of 1781 genes were differentially expressed between samples cultured under normal and PEG-induced drought stress conditions.Similar to those in drought resistance plants and non-lichenized fungi,the common drought-resistant mechanisms were differentially expressed in E.pusillum.However,the expression change of genes involved in osmotic regulation in E.pusillum is different,which might be the evidence for the feature of drought adaptation.Interestingly,different from other organisms,some genes involved in drought adaption mechanisms showed significantly different expression patterns between the presence and absence of drought stress in E.pusillum.The expression of 23 candidate stress responsive genes was further confirmed by quantitative real-time PCR using dehydrated E.pusillum lichen thalli.This study provides a valuable resource for future research on lichen-forming fungi and shall facilitate future functional studies of the specific genes related to drought resistance.
基金supported by the International Science and Technology Cooperation of China(2011DFA32730)
文摘Panax ginseng C. A. Meyer is an important traditional herb in eastern Asia. It contains ginsenosides, which are primary bioactive compounds with medicinal properties. Although ginseng has been cultivated since at least the Ming dynasty to increase production, cultivated ginseng has lower quantities of ginsenosides and lower disease resistance than ginseng grown under natural conditions. We extracted root RNA from six varieties of fifth-year P. ginseng cultivars representing four different growth conditions, and performed Illumina paired-end sequencing. In total, 163,165,706 raw reads were obtained and used to generate a de novo transcriptome that consisted of 151,763 contigs(76,336 unigenes), of which 100,648 contigs(66.3%) were successfully annotated. Differential expression analysis revealed that most differentially expressed genes(DEGs) were upregulated(246 out of 258, 95.3%) in ginseng grown under natural conditions compared with that grown under artificial conditions. These DEGs were enriched in gene ontology(GO) terms including response to stimuli and localization. In particular, some key ginsenoside biosynthesis-related genes, including HMG-Co A synthase(HMGS), mevalonate kinase(MVK), and squalene epoxidase(SE), were upregulated in wild-grown ginseng. Moreover, a high proportion of disease resistance-related genes were upregulated in wild-grown ginseng. This study is the first transcriptome analysis to compare wild-grown and cultivated ginseng, and identifies genes that may produce higher ginsenoside content and better disease resistance in the wild; these genes may have the potential to improve cultivated ginseng grown in artificial environments.
基金supported by the Queensland-Chinese Academy of Sciences(QCAS)Biotechnology Fund(GJHZ1131)the Project of Chinese Academy of Sciences for the Development of Major Scientific Research Equipment(YZ201148)+1 种基金the National Natural Science Foundation of China(31200628)the External Cooperation Program of Bureau of International Cooperation,Chinese Academy of Sciences(GJHZ201302)
文摘Research has shown that the hypomagnetic field(HMF)can affect embryo development,cell proliferation,learning and memory,and in vitro tubulin assembly.In the present study,we aimed to elucidate the molecular mechanism by which the HMF exerts its effect,by comparing the transcriptome profiles of human neuroblastoma cells exposed to either the HMF or the geomagnetic field.A total of 2464 differentially expressed genes(DEGs)were identified,216 of which were up-regulated and2248 of which were down-regulated after exposure to the HMF.These DEGs were found to be significantly clustered into several key processes,namely macromolecule localization,protein transport,RNA processing,and brain function.Seventeen DEGs were verified by real-time quantitative PCR,and the expression levels of nine of these DEGs were measured every 6 h.Most notably,MAPK1 and CRY2,showed significant up-and down-regulation,respectively,during the first 6 h of HMF exposure,which suggests involvement of the MAPK pathway and cryptochrome in the early bio-HMF response.Our results provide insights into the molecular mechanisms underlying the observed biological effects of the HMF.