How Microbes Shape Their Communities? A Microbial Community Model Based on Functional Genes
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摘要
Exploring the mechanisms of maintaining microbial community structure is important to understand biofilm development or microbiota dysbiosis. In this paper, we propose a functional gene-based composition prediction(FCP) model to predict the population structure composition within a microbial community. The model predicts the community composition well in both a low-complexity community as acid mine drainage(AMD) microbiota, and a complex community as human gut microbiota. Furthermore, we define community structure shaping(CSS) genes as functional genes crucial for shaping the microbial community. We have identified CSS genes in AMD and human gut microbiota samples with FCP model and find that CSS genes change with the conditions. Compared to essential genes for microbes, CSS genes are significantly enriched in the genes involved in mobile genetic elements, cell motility, and defense mechanisms, indicating that the functions of CSS genes are focused on communication and strategies in response to the environment factors. We further find that it is the minority, rather than the majority, which contributes to maintaining community structure. Compared to health control samples, we find that some functional genes associated with metabolism of amino acids, nucleotides, and lipopolysaccharide are more likely to be CSS genes in the disease group. CSS genes may help us to understand critical cellular processes and be useful in seeking addable gene circuitries to maintain artificial self-sustainable communities. Our study suggests that functional genes are important to the assembly of microbial communities.
Exploring the mechanisms of maintaining microbial community structure is important to understand biofilm development or microbiota dysbiosis. In this paper, we propose a functional gene-based composition prediction(FCP) model to predict the population structure composition within a microbial community. The model predicts the community composition well in both a low-complexity community as acid mine drainage(AMD) microbiota, and a complex community as human gut microbiota. Furthermore, we define community structure shaping(CSS) genes as functional genes crucial for shaping the microbial community. We have identified CSS genes in AMD and human gut microbiota samples with FCP model and find that CSS genes change with the conditions. Compared to essential genes for microbes, CSS genes are significantly enriched in the genes involved in mobile genetic elements, cell motility, and defense mechanisms, indicating that the functions of CSS genes are focused on communication and strategies in response to the environment factors. We further find that it is the minority, rather than the majority, which contributes to maintaining community structure. Compared to health control samples, we find that some functional genes associated with metabolism of amino acids, nucleotides, and lipopolysaccharide are more likely to be CSS genes in the disease group. CSS genes may help us to understand critical cellular processes and be useful in seeking addable gene circuitries to maintain artificial self-sustainable communities. Our study suggests that functional genes are important to the assembly of microbial communities.
Exploring the mechanisms of maintaining microbial community structure is important to understand biofilm development or microbiota dysbiosis. In this paper, we propose a functional gene-based composition prediction(FCP) model to predict the population structure composition within a microbial community. The model predicts the community composition well in both a low-complexity community as acid mine drainage(AMD) microbiota, and a complex community as human gut microbiota. Furthermore, we define community structure shaping(CSS) genes as functional genes crucial for shaping the microbial community. We have identified CSS genes in AMD and human gut microbiota samples with FCP model and find that CSS genes change with the conditions. Compared to essential genes for microbes, CSS genes are significantly enriched in the genes involved in mobile genetic elements, cell motility, and defense mechanisms, indicating that the functions of CSS genes are focused on communication and strategies in response to the environment factors. We further find that it is the minority, rather than the majority, which contributes to maintaining community structure. Compared to health control samples, we find that some functional genes associated with metabolism of amino acids, nucleotides, and lipopolysaccharide are more likely to be CSS genes in the disease group. CSS genes may help us to understand critical cellular processes and be useful in seeking addable gene circuitries to maintain artificial self-sustainable communities. Our study suggests that functional genes are important to the assembly of microbial communities.
引文
[1]Larsen P,Hamada Y,Gilbert J.Modeling microbial communities:current,developing,and future technologies for predicting microbial community interaction.J Biotechnol 2012;160:17-24.
[2]Gilbert JA,Dupont CL.Microbial metagenomics:beyond the genome.Annu Rev Mar Sci 2011;3:347-71.
[3]Fuhrman JA.Microbial community structure and its functional implications.Nature 2009;459:193-9.
[4]Burke C,Steinberg P,Rusch D,Kjelleberg S,Thomas T.Bacterial community assembly based on functional genes rather than species.Proc Natl Acad Sci U S A 2011;108:14288-93.
[5]Almeida WI,Vieira RP,Cardoso AM,Silveira CB,Costa RG,Gonzalez AM,et al.Archaeal and bacterial communities of heavy metal contaminated acidic waters from zinc mine residues in Sepetiba Bay.Extremophiles 2009;2:263-71.
[6]Stojanovic′MR,Biagi E,Heilig HGHJ,Kajander K,Kekkonen RA,Tims S,et al.Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome.Gastroenterology 2011;5:1792-801.
[7]Ng SC,Lam EFC,Lam TTY,Chan Y,Law W,Tse PCH,et al.Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome.J Gastroenterol Hepatol 2013;10:1624-31.
[8]Jeffery IB,O’Toole PW,O¨hman L,Claesson MJ,Deane J,Quigley EMM,et al.An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota.Gut2012;7:997-1006.
[9]Naseribafrouei A,Hestad K,Avershina E,Sekelja M,Linl?kken A,Wilson R,et al.Correlation between the human fecal microbiota and depression.Neurogastroenterol Motil2014;8:1155-62.
[10]Jeffreys B,Johnr T,Danielp R,Ingaa Z,Judee M.Factors affecting soil microbial community structure in tomato cropping systems.Soil Biol Biochem 2010;42:831-41.
[11]Wei L,Shutao W,Jin Z,Tong X.Biochar influences the microbial community structure during tomato stalk composting with chicken manure.Bioresour Technol 2014;154:148-54.
[12]Aciego Pietri JC,Brookes PC.Substrate inputs and pH as factors controlling microbial biomass,activity and community structure in an arable soil.Soil Biol Biochem 2009;41:1396-405.
[13]Maspolim Y,Zhou Y,Guo C,Xiao K,Ng WJ.The effect of p Hon solubilization of organic matter and microbial community structures in sludge fermentation.Bioresour Technol2015;190:289-98.
[14]Wellborn GA,Skelly DK,Werner EE.Mechanisms creating community structure across a freshwater habitat gradient.Annu Rev Ecol Syst 1996;27:337-63.
[15]Luo H,Lin Y,Gao F,Zhang C,Zhang R.DEG 10,an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements.Nucleic Acids Res2013;42:D574-80.
[16]De Y,Dong C,Cao Y,Wang X,Yang X.Genome-wide sequence transposon insertion sites and analyze the essential genes of Brucella melitensis.Microb Pathog 2017;112:97-102.
[17]Goodman AL,McNulty NP,Zhao Y,Leip D,Mitra RD,Lozupone CA,et al.Identifying genetic determinants needed to establish a human gut symbiont in its habitat.Cell Host Microbe2009;6:279-89.
[18]Zhang YJ,Ioerger TR,Huttenhower C,Long JE,Sassetti CM,Sacchettini JC,et al.Global assessment of genomic regions required for growth in Mycobacterium tuberculosis.PLoS Pathog2012;8:e1002946.
[19]Minkenberg B,Xie K,Yang Y.Discovery of rice essential genes by characterizing a CRISPR-edited mutation of closely related rice MAP kinase genes.Plant J 2017;89:636-48.
[20]Larsen PE,Gibbons SM,Gilbert JA.Modeling microbial community structure and functional diversity across time and space.FEMS Microbiol Lett 2012;332:91-8.
[21]Larsen PE,Field D,Gilbert JA.Predicting bacterial community assemblages using an artificial neural network approach.Nat Methods 2012;9:621-5.
[22]Stein RR,Bucci V,Toussaint NC,Buffie CG,Ratsch G,Pamer EG,et al.Ecological modeling from time-series inference:insight into dynamics and stability of intestinal microbiota.PLoSComput Biol 2013;9:e1003388.
[23]Marino S,Baxter NT,Huffnagle GB,Petrosino JF,Schloss PD.Mathematical modeling of primary succession of murine intestinal microbiota.Proc Natl Acad Sci U S A 2014;111:439-44.
[24]Trosvik P,Rudi K,Naes T,Kohler A,Chan KS,Jakobsen KS,et al.Characterizing mixed microbial population dynamics using time-series analysis.ISME J 2008;2:707-15.
[25]Trosvik P,Stenseth NC,Rudi K.Convergent temporal dynamics of the human infant gut microbiota.ISME J 2010;4:151-8.
[26]Gerber GK.The dynamic microbiome.FEBS Lett2014;588:4131-9.
[27]Schuster P,Sigmund K.Replicator dynamics.J Theor Biol1983;100:533-8.
[28]Li X,Pietschke C,Fraune S,Altrock PM,Bosch TCG,Traulsen A.Which games are growing bacterial populations playing?J RSoc Interface 2015;12:20150121.
[29]Eyre-Walker A,Keightley PD.The distribution of fitness effects of new mutations.Nat Rev Genet 2007;8:610-8.
[30]Laughlin DC,Joshi C,van Bodegom PM,Bastow ZA,Fule′PZ.Apredictive model of community assembly that incorporates intraspecific trait variation.Ecol Lett 2012;15:1291-9.
[31]Guo J,Wang Q,Wang X,Wang F,Yao J,Zhu H.Horizontal gene transfer in an acid mine drainage microbial community.BMC Genomics 2015;16:496.
[32]Mueller RS,Denef VJ,Kalnejais LH,Suttle KB,Thomas BC,Wilmes P,et al.Ecological distribution and population physiology defined by proteomics in a natural microbial community.Mol Syst Biol 2010;6:374.
[33]Galperin MY,Makarova KS,Wolf YI,Koonin EV.Expanded microbial genome coverage and improved protein family annotation in the COG database.Nucleic Acids Res 2014;43:D261-9.
[34]De’ath G.Multivariate regression trees:a new technique for modeling species-environment relationship.Ecology2002;83:1105-17.
[35]Natekin A,Knoll A.Gradient boosting machines,a tutorial.Front Neurorobot 2013;7:21.
[36]Kuang J,Huang L,Chen L,Hua Z,Li S,Hu M,et al.Contemporary environmental variation determines microbial diversity patterns in acid mine drainage.ISME J 2013;7:1038-50.
[37]Spiller R,Aziz Q,Creed F,Houghton L,Hungin P,Jones R,et al.Guidelines on the irritable bowel syndrome:mechanisms and practical management.Gut 2007;56:1770-98.
[38]Liu Y,Zhang L,Wang X,Wang Z,Zhang J,Jiang R,et al.Similar fecal microbiota signatures in patients with diarrheapredominant irritable bowel syndrome and patients with depression.Clin Gastroenterol Hepatol 2016;14:1602-11.
[39]Cryan JF,Dinan TG.More than a gut feeling:the microbiota regulates neurodevelopment and behavior.Neuropsychopharmacology 2015;40:241.
[40]Mendiola MV,Bernales I,De L.Differential roles of the transposon termini in IS91 transposition.Proc Natl Acad Sci US A 1994;91:1922-6.
[41]Benjak A,Forneck A,Casacuberta JM.Genome-wide analysis of the‘‘cut-and-paste”transposons of grapevine.PLoS One2008;3:14-24.
[42]Jalanka-Tuovinen J,Saloja¨rvi J,Salonen A,Immonen O,Garsed K,Kelly FM,et al.Faecal microbiota composition and hostmicrobe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome.Gut 2014;11:1737.
[43]McCauley R,Kong SE,Hall J.Glutamine and nucleotide metabolism within enterocytes.JPEN J Parenter Enteral Nutr1998;2:105-11.
[44]Ma Z,Liu H,Wu B.Structure-based drug design of catechol-O-methyltransferase inhibitors for CNS disorders.Br J Clin Pharmacol 2014;3:410-20.
[45]Tunbridge EM,Bannerman DM,Sharp T,Harrison PJ.CatecholO-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex.J Neurosci 2004;23:5331-5.
[46]Aberg E,Fandin?o-Losada A,Sjo¨holm LK,Al E.The functional Val158Met polymorphism in catechol-O-methyltransferase(COMT)is associated with depression and motivation in men from a Swedish population-based study.J Affect Disord 2011;1:158-66.
[47]Webb CT,Hoeting JA,Ames GM,Pyne MI,Poff NLR.Astructured and dynamic framework to advance traits-based theory and prediction in ecology.Ecol Lett 2010;13:267-83.
[48]Laliberte′E,Shipley B,Norton DA,Scott D.Which plant traits determine abundance under long-term shifts in soil resource availability and grazing intensity?J Ecol 2012;100:662-77.
[49]Allen EE,Bartlett DH.Structure and regulation of the omega-3polyunsaturated fatty acid synthase genes from the deep-sea bacterium Photobacterium profundum strain SS9.Microbiology2002;148:1903-13.
[50]Mischoulon DFM.Role of S-adenosyl-L-methionine in the treatment of depression:a review of the evidence.Am J Clin Nutr 2002;5:1158-61.
[51]Bressa GM.S-adenosyl-L-methionine(SAMe)as antidepressant:meta-analysis of clinical studies.Acta Neurol Scand 1994;S154:7-14.
[52]Kelley DR,Schatz MC,Salzberg SL.Quake:quality-aware detection and correction of sequencing errors.Genome Biol2010;11:R116.
[53]Schmieder R,Edwards R.Quality control and preprocessing of metagenomic datasets.Bioinformatics 2011;6:863-4.
[54]Lai B,Wang F,Wang X,Duan L,Zhu H.InteMAP:Integrated metagenomic assembly pipeline for NGS short reads.BMCBioinformatics 2015;1:244.
[55]Liu Y,Guo J,Hu G,Zhu H.Gene prediction in metagenomic fragments based on the SVM algorithm.BMC Bioinformatics2013;14:S12.
[56]Hu G,Guo J,Liu Y,Zhu H.MetaTISA:metagenomic translation initiation site annotator for improving gene start prediction.Bioinformatics 2009;25:1843-5.
[57]Brady A,Salzberg SL.Phymm and PhymmBL:metagenomic phylogenetic classification with interpolated Markov models.Nat Methods 2009;6:673-6.
[58]Brady A,Salzberg S.PhymmBL expanded:confidence scores,custom databases,parallelization and more.Nat Methods2011;8:367.
[59]Tatusov RL,Fedorova ND,Jackson JD,Jacobs AR,Kiryutin B,Koonin EV,et al.The COG database:an updated version includes eukaryotes.BMC Bioinformatics 2003;4:41.
[60]Tatusov R,Galperin M,Natale D,Koonin EV.The COGdatabase:a tool for genome-scale analysis of protein functions and evolution.Nucleic Acids Res 2000;1:33-6.
[61]Altschul S,Gish W,Miller W,Myers EW,Lipman DJ.Basic local alignment search tool.J Mol Biol 1990;3:403-10.
[62]Shannon P,Markiel A,Ozier O,Baliga NS,Wang JT,Ramage D,et al.Cytoscape:a software environment for integrated models of biomolecular interaction networks.Genome Res2003;13:2498-504.
[63]Hoehler TM,J?rgensen BB.Microbial life under extreme energy limitation.Nat Rev Microbiol 2013;11:83-94.
[2]Gilbert JA,Dupont CL.Microbial metagenomics:beyond the genome.Annu Rev Mar Sci 2011;3:347-71.
[3]Fuhrman JA.Microbial community structure and its functional implications.Nature 2009;459:193-9.
[4]Burke C,Steinberg P,Rusch D,Kjelleberg S,Thomas T.Bacterial community assembly based on functional genes rather than species.Proc Natl Acad Sci U S A 2011;108:14288-93.
[5]Almeida WI,Vieira RP,Cardoso AM,Silveira CB,Costa RG,Gonzalez AM,et al.Archaeal and bacterial communities of heavy metal contaminated acidic waters from zinc mine residues in Sepetiba Bay.Extremophiles 2009;2:263-71.
[6]Stojanovic′MR,Biagi E,Heilig HGHJ,Kajander K,Kekkonen RA,Tims S,et al.Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome.Gastroenterology 2011;5:1792-801.
[7]Ng SC,Lam EFC,Lam TTY,Chan Y,Law W,Tse PCH,et al.Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome.J Gastroenterol Hepatol 2013;10:1624-31.
[8]Jeffery IB,O’Toole PW,O¨hman L,Claesson MJ,Deane J,Quigley EMM,et al.An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota.Gut2012;7:997-1006.
[9]Naseribafrouei A,Hestad K,Avershina E,Sekelja M,Linl?kken A,Wilson R,et al.Correlation between the human fecal microbiota and depression.Neurogastroenterol Motil2014;8:1155-62.
[10]Jeffreys B,Johnr T,Danielp R,Ingaa Z,Judee M.Factors affecting soil microbial community structure in tomato cropping systems.Soil Biol Biochem 2010;42:831-41.
[11]Wei L,Shutao W,Jin Z,Tong X.Biochar influences the microbial community structure during tomato stalk composting with chicken manure.Bioresour Technol 2014;154:148-54.
[12]Aciego Pietri JC,Brookes PC.Substrate inputs and pH as factors controlling microbial biomass,activity and community structure in an arable soil.Soil Biol Biochem 2009;41:1396-405.
[13]Maspolim Y,Zhou Y,Guo C,Xiao K,Ng WJ.The effect of p Hon solubilization of organic matter and microbial community structures in sludge fermentation.Bioresour Technol2015;190:289-98.
[14]Wellborn GA,Skelly DK,Werner EE.Mechanisms creating community structure across a freshwater habitat gradient.Annu Rev Ecol Syst 1996;27:337-63.
[15]Luo H,Lin Y,Gao F,Zhang C,Zhang R.DEG 10,an update of the database of essential genes that includes both protein-coding genes and noncoding genomic elements.Nucleic Acids Res2013;42:D574-80.
[16]De Y,Dong C,Cao Y,Wang X,Yang X.Genome-wide sequence transposon insertion sites and analyze the essential genes of Brucella melitensis.Microb Pathog 2017;112:97-102.
[17]Goodman AL,McNulty NP,Zhao Y,Leip D,Mitra RD,Lozupone CA,et al.Identifying genetic determinants needed to establish a human gut symbiont in its habitat.Cell Host Microbe2009;6:279-89.
[18]Zhang YJ,Ioerger TR,Huttenhower C,Long JE,Sassetti CM,Sacchettini JC,et al.Global assessment of genomic regions required for growth in Mycobacterium tuberculosis.PLoS Pathog2012;8:e1002946.
[19]Minkenberg B,Xie K,Yang Y.Discovery of rice essential genes by characterizing a CRISPR-edited mutation of closely related rice MAP kinase genes.Plant J 2017;89:636-48.
[20]Larsen PE,Gibbons SM,Gilbert JA.Modeling microbial community structure and functional diversity across time and space.FEMS Microbiol Lett 2012;332:91-8.
[21]Larsen PE,Field D,Gilbert JA.Predicting bacterial community assemblages using an artificial neural network approach.Nat Methods 2012;9:621-5.
[22]Stein RR,Bucci V,Toussaint NC,Buffie CG,Ratsch G,Pamer EG,et al.Ecological modeling from time-series inference:insight into dynamics and stability of intestinal microbiota.PLoSComput Biol 2013;9:e1003388.
[23]Marino S,Baxter NT,Huffnagle GB,Petrosino JF,Schloss PD.Mathematical modeling of primary succession of murine intestinal microbiota.Proc Natl Acad Sci U S A 2014;111:439-44.
[24]Trosvik P,Rudi K,Naes T,Kohler A,Chan KS,Jakobsen KS,et al.Characterizing mixed microbial population dynamics using time-series analysis.ISME J 2008;2:707-15.
[25]Trosvik P,Stenseth NC,Rudi K.Convergent temporal dynamics of the human infant gut microbiota.ISME J 2010;4:151-8.
[26]Gerber GK.The dynamic microbiome.FEBS Lett2014;588:4131-9.
[27]Schuster P,Sigmund K.Replicator dynamics.J Theor Biol1983;100:533-8.
[28]Li X,Pietschke C,Fraune S,Altrock PM,Bosch TCG,Traulsen A.Which games are growing bacterial populations playing?J RSoc Interface 2015;12:20150121.
[29]Eyre-Walker A,Keightley PD.The distribution of fitness effects of new mutations.Nat Rev Genet 2007;8:610-8.
[30]Laughlin DC,Joshi C,van Bodegom PM,Bastow ZA,Fule′PZ.Apredictive model of community assembly that incorporates intraspecific trait variation.Ecol Lett 2012;15:1291-9.
[31]Guo J,Wang Q,Wang X,Wang F,Yao J,Zhu H.Horizontal gene transfer in an acid mine drainage microbial community.BMC Genomics 2015;16:496.
[32]Mueller RS,Denef VJ,Kalnejais LH,Suttle KB,Thomas BC,Wilmes P,et al.Ecological distribution and population physiology defined by proteomics in a natural microbial community.Mol Syst Biol 2010;6:374.
[33]Galperin MY,Makarova KS,Wolf YI,Koonin EV.Expanded microbial genome coverage and improved protein family annotation in the COG database.Nucleic Acids Res 2014;43:D261-9.
[34]De’ath G.Multivariate regression trees:a new technique for modeling species-environment relationship.Ecology2002;83:1105-17.
[35]Natekin A,Knoll A.Gradient boosting machines,a tutorial.Front Neurorobot 2013;7:21.
[36]Kuang J,Huang L,Chen L,Hua Z,Li S,Hu M,et al.Contemporary environmental variation determines microbial diversity patterns in acid mine drainage.ISME J 2013;7:1038-50.
[37]Spiller R,Aziz Q,Creed F,Houghton L,Hungin P,Jones R,et al.Guidelines on the irritable bowel syndrome:mechanisms and practical management.Gut 2007;56:1770-98.
[38]Liu Y,Zhang L,Wang X,Wang Z,Zhang J,Jiang R,et al.Similar fecal microbiota signatures in patients with diarrheapredominant irritable bowel syndrome and patients with depression.Clin Gastroenterol Hepatol 2016;14:1602-11.
[39]Cryan JF,Dinan TG.More than a gut feeling:the microbiota regulates neurodevelopment and behavior.Neuropsychopharmacology 2015;40:241.
[40]Mendiola MV,Bernales I,De L.Differential roles of the transposon termini in IS91 transposition.Proc Natl Acad Sci US A 1994;91:1922-6.
[41]Benjak A,Forneck A,Casacuberta JM.Genome-wide analysis of the‘‘cut-and-paste”transposons of grapevine.PLoS One2008;3:14-24.
[42]Jalanka-Tuovinen J,Saloja¨rvi J,Salonen A,Immonen O,Garsed K,Kelly FM,et al.Faecal microbiota composition and hostmicrobe cross-talk following gastroenteritis and in postinfectious irritable bowel syndrome.Gut 2014;11:1737.
[43]McCauley R,Kong SE,Hall J.Glutamine and nucleotide metabolism within enterocytes.JPEN J Parenter Enteral Nutr1998;2:105-11.
[44]Ma Z,Liu H,Wu B.Structure-based drug design of catechol-O-methyltransferase inhibitors for CNS disorders.Br J Clin Pharmacol 2014;3:410-20.
[45]Tunbridge EM,Bannerman DM,Sharp T,Harrison PJ.CatecholO-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex.J Neurosci 2004;23:5331-5.
[46]Aberg E,Fandin?o-Losada A,Sjo¨holm LK,Al E.The functional Val158Met polymorphism in catechol-O-methyltransferase(COMT)is associated with depression and motivation in men from a Swedish population-based study.J Affect Disord 2011;1:158-66.
[47]Webb CT,Hoeting JA,Ames GM,Pyne MI,Poff NLR.Astructured and dynamic framework to advance traits-based theory and prediction in ecology.Ecol Lett 2010;13:267-83.
[48]Laliberte′E,Shipley B,Norton DA,Scott D.Which plant traits determine abundance under long-term shifts in soil resource availability and grazing intensity?J Ecol 2012;100:662-77.
[49]Allen EE,Bartlett DH.Structure and regulation of the omega-3polyunsaturated fatty acid synthase genes from the deep-sea bacterium Photobacterium profundum strain SS9.Microbiology2002;148:1903-13.
[50]Mischoulon DFM.Role of S-adenosyl-L-methionine in the treatment of depression:a review of the evidence.Am J Clin Nutr 2002;5:1158-61.
[51]Bressa GM.S-adenosyl-L-methionine(SAMe)as antidepressant:meta-analysis of clinical studies.Acta Neurol Scand 1994;S154:7-14.
[52]Kelley DR,Schatz MC,Salzberg SL.Quake:quality-aware detection and correction of sequencing errors.Genome Biol2010;11:R116.
[53]Schmieder R,Edwards R.Quality control and preprocessing of metagenomic datasets.Bioinformatics 2011;6:863-4.
[54]Lai B,Wang F,Wang X,Duan L,Zhu H.InteMAP:Integrated metagenomic assembly pipeline for NGS short reads.BMCBioinformatics 2015;1:244.
[55]Liu Y,Guo J,Hu G,Zhu H.Gene prediction in metagenomic fragments based on the SVM algorithm.BMC Bioinformatics2013;14:S12.
[56]Hu G,Guo J,Liu Y,Zhu H.MetaTISA:metagenomic translation initiation site annotator for improving gene start prediction.Bioinformatics 2009;25:1843-5.
[57]Brady A,Salzberg SL.Phymm and PhymmBL:metagenomic phylogenetic classification with interpolated Markov models.Nat Methods 2009;6:673-6.
[58]Brady A,Salzberg S.PhymmBL expanded:confidence scores,custom databases,parallelization and more.Nat Methods2011;8:367.
[59]Tatusov RL,Fedorova ND,Jackson JD,Jacobs AR,Kiryutin B,Koonin EV,et al.The COG database:an updated version includes eukaryotes.BMC Bioinformatics 2003;4:41.
[60]Tatusov R,Galperin M,Natale D,Koonin EV.The COGdatabase:a tool for genome-scale analysis of protein functions and evolution.Nucleic Acids Res 2000;1:33-6.
[61]Altschul S,Gish W,Miller W,Myers EW,Lipman DJ.Basic local alignment search tool.J Mol Biol 1990;3:403-10.
[62]Shannon P,Markiel A,Ozier O,Baliga NS,Wang JT,Ramage D,et al.Cytoscape:a software environment for integrated models of biomolecular interaction networks.Genome Res2003;13:2498-504.
[63]Hoehler TM,J?rgensen BB.Microbial life under extreme energy limitation.Nat Rev Microbiol 2013;11:83-94.