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==History==
 
==History==
 
The study of network motifs was pioneered by Holland and Leinhardt<ref>Holland, P. W., & Leinhardt, S. (1974). The statistical analysis of local structure in social networks. Working Paper No. 44, National Bureau of Economic Research.</ref><ref>Hollandi, P., & Leinhardt, S. (1975). The Statistical Analysis of Local. Structure in Social Networks. Sociological Methodology, David Heise, ed. San Francisco: Josey-Bass.</ref><ref> Holland, P. W., & Leinhardt, S. (1976). Local structure in social networks. Sociological methodology, 7, 1-45.</ref><ref>Holland, P. W., & Leinhardt, S. (1977). A method for detecting structure in sociometric data. In Social Networks (pp. 411-432). Academic Press.</ref> who introduced the concept of a triad census of networks. They introduced methods to enumerate various types of subgraph configurations, and test whether the subgraph counts are statistically different from those expected in random networks.  
 
The study of network motifs was pioneered by Holland and Leinhardt<ref>Holland, P. W., & Leinhardt, S. (1974). The statistical analysis of local structure in social networks. Working Paper No. 44, National Bureau of Economic Research.</ref><ref>Hollandi, P., & Leinhardt, S. (1975). The Statistical Analysis of Local. Structure in Social Networks. Sociological Methodology, David Heise, ed. San Francisco: Josey-Bass.</ref><ref> Holland, P. W., & Leinhardt, S. (1976). Local structure in social networks. Sociological methodology, 7, 1-45.</ref><ref>Holland, P. W., & Leinhardt, S. (1977). A method for detecting structure in sociometric data. In Social Networks (pp. 411-432). Academic Press.</ref> who introduced the concept of a triad census of networks. They introduced methods to enumerate various types of subgraph configurations, and test whether the subgraph counts are statistically different from those expected in random networks.  
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霍兰(Holland)和莱因哈特(Leinhardt)率先提出了'''网络三合会普查'''(a triad census of networks)的概念,开创了网络模体研究的先河。<ref>Holland, P. W., & Leinhardt, S. (1974). The statistical analysis of local structure in social networks. Working Paper No. 44, National Bureau of Economic Research.</ref><ref>Hollandi, P., & Leinhardt, S. (1975). The Statistical Analysis of Local. Structure in Social Networks. Sociological Methodology, David Heise, ed. San Francisco: Josey-Bass.</ref><ref> Holland, P. W., & Leinhardt, S. (1976). Local structure in social networks. Sociological methodology, 7, 1-45.</ref><ref>Holland, P. W., & Leinhardt, S. (1977). A method for detecting structure in sociometric data. In Social Networks (pp. 411-432). Academic Press.</ref>他们介绍了枚举各种子图配置的方法,并测试子图计数是否与随机网络中的期望值存在统计学上的差异。
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这里对于'''网络三合会普查'''(a triad census of networks)这一概念的翻译存疑
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This idea was further generalized in 2002 by [[Uri Alon]] and his group <ref name="she1">{{cite journal |vauthors=Shen-Orr SS, Milo R, Mangan S, Alon U |title=Network motifs in the transcriptional regulation network of ''Escherichia coli'' |journal=Nat. Genet. |volume=31 |issue=1 |pages=64–8 |date=May 2002 |pmid=11967538 |doi=10.1038/ng881}}</ref> when network motifs were discovered in the gene regulation (transcription) network of the bacteria ''[[Escherichia coli|E. coli]]'' and then in a large set of natural networks. Since then, a considerable number of studies have been conducted on the subject. Some of these studies focus on the biological applications, while others focus on the computational theory of network motifs.
 
This idea was further generalized in 2002 by [[Uri Alon]] and his group <ref name="she1">{{cite journal |vauthors=Shen-Orr SS, Milo R, Mangan S, Alon U |title=Network motifs in the transcriptional regulation network of ''Escherichia coli'' |journal=Nat. Genet. |volume=31 |issue=1 |pages=64–8 |date=May 2002 |pmid=11967538 |doi=10.1038/ng881}}</ref> when network motifs were discovered in the gene regulation (transcription) network of the bacteria ''[[Escherichia coli|E. coli]]'' and then in a large set of natural networks. Since then, a considerable number of studies have been conducted on the subject. Some of these studies focus on the biological applications, while others focus on the computational theory of network motifs.
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2002年,Uri Alon和他的团队[17]在大肠杆菌的基因调控(gene regulation network)(转录 transcription)网络中发现了网络模体,随后在大量的自然网络中也发现了网络模体,从而进一步推广了这一观点。自那时起,许多科学家都对这一问题进行了大量的研究。其中一些研究集中在生物学应用上,而另一些则集中在网络模体的计算理论上。<ref name="she1">{{cite journal |vauthors=Shen-Orr SS, Milo R, Mangan S, Alon U |title=Network motifs in the transcriptional regulation network of ''Escherichia coli'' |journal=Nat. Genet. |volume=31 |issue=1 |pages=64–8 |date=May 2002 |pmid=11967538 |doi=10.1038/ng881}}</ref>
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The biological studies endeavor to interpret the motifs detected for biological networks. For example, in work following,<ref name="she1" /> the network motifs found in ''[[Escherichia coli|E. coli]]'' were discovered in the transcription networks of other bacteria<ref name="eic1">{{cite journal  |vauthors=Eichenberger P, Fujita M, Jensen ST, etal |title=The program of gene transcription for a single differentiating cell type during sporulation in ''Bacillus subtilis'' |journal=PLOS Biology |volume=2 |issue=10 |pages=e328 |date=October 2004 |pmid=15383836 |pmc=517825 |doi=10.1371/journal.pbio.0020328 }} {{open access}}</ref> as well as yeast<ref name="mil3">{{cite journal |vauthors=Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U |title=Network motifs: simple building blocks of complex networks |journal=Science |volume=298 |issue=5594 |pages=824–7 |date=October 2002 |doi=10.1126/science.298.5594.824 |pmid=12399590|bibcode=2002Sci...298..824M |citeseerx=10.1.1.225.8750 }}</ref><ref name="lee1">{{cite journal  |vauthors=Lee TI, Rinaldi NJ, Robert F, etal |title=Transcriptional regulatory networks in Saccharomyces cerevisiae |journal=Science |volume=298 |issue=5594 |pages=799–804 |date=October 2002 |pmid=12399584 |doi=10.1126/science.1075090 |bibcode=2002Sci...298..799L }}</ref> and higher organisms.<ref name="odo1">{{cite journal  |vauthors=Odom DT, Zizlsperger N, Gordon DB, etal |title=Control of pancreas and liver gene expression by HNF transcription factors |journal=Science |volume=303 |issue=5662 |pages=1378–81 |date=February 2004 |pmid=14988562 |pmc=3012624 |doi=10.1126/science.1089769 |bibcode=2004Sci...303.1378O }}</ref><ref name="boy1">{{cite journal  |vauthors=Boyer LA, Lee TI, Cole MF, etal |title=Core transcriptional regulatory circuitry in human embryonic stem cells |journal=Cell |volume=122 |issue=6 |pages=947–56 |date=September 2005 |pmid=16153702 |pmc=3006442 |doi=10.1016/j.cell.2005.08.020 }}</ref><ref name="ira1">{{cite journal |vauthors=Iranfar N, Fuller D, Loomis WF |title=Transcriptional regulation of post-aggregation genes in Dictyostelium by a feed-forward loop involving GBF and LagC |journal=Dev. Biol. |volume=290 |issue=2 |pages=460–9 |date=February 2006 |pmid=16386729 |doi=10.1016/j.ydbio.2005.11.035 |doi-access=free }}</ref> A distinct set of network motifs were identified in other types of biological networks such as neuronal networks and protein interaction networks.<ref name="mil2" /><ref name="maa1">{{cite journal  |vauthors=Ma'ayan A, Jenkins SL, Neves S, etal |title=Formation of regulatory patterns during signal propagation in a Mammalian cellular network |journal=Science |volume=309 |issue=5737 |pages=1078–83 |date=August 2005 |pmid=16099987 |pmc=3032439 |doi=10.1126/science.1108876 |bibcode=2005Sci...309.1078M }}</ref><ref name="pta1">{{cite journal  |vauthors=Ptacek J, Devgan G, Michaud G, etal |title=Global analysis of protein phosphorylation in yeast |journal=Nature |volume=438 |issue=7068 |pages=679–84 |date=December 2005 |pmid=16319894 |doi=10.1038/nature04187|bibcode=2005Natur.438..679P |url=https://authors.library.caltech.edu/56271/2/Tables.pdf |type=Submitted manuscript }}</ref>
 
The biological studies endeavor to interpret the motifs detected for biological networks. For example, in work following,<ref name="she1" /> the network motifs found in ''[[Escherichia coli|E. coli]]'' were discovered in the transcription networks of other bacteria<ref name="eic1">{{cite journal  |vauthors=Eichenberger P, Fujita M, Jensen ST, etal |title=The program of gene transcription for a single differentiating cell type during sporulation in ''Bacillus subtilis'' |journal=PLOS Biology |volume=2 |issue=10 |pages=e328 |date=October 2004 |pmid=15383836 |pmc=517825 |doi=10.1371/journal.pbio.0020328 }} {{open access}}</ref> as well as yeast<ref name="mil3">{{cite journal |vauthors=Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U |title=Network motifs: simple building blocks of complex networks |journal=Science |volume=298 |issue=5594 |pages=824–7 |date=October 2002 |doi=10.1126/science.298.5594.824 |pmid=12399590|bibcode=2002Sci...298..824M |citeseerx=10.1.1.225.8750 }}</ref><ref name="lee1">{{cite journal  |vauthors=Lee TI, Rinaldi NJ, Robert F, etal |title=Transcriptional regulatory networks in Saccharomyces cerevisiae |journal=Science |volume=298 |issue=5594 |pages=799–804 |date=October 2002 |pmid=12399584 |doi=10.1126/science.1075090 |bibcode=2002Sci...298..799L }}</ref> and higher organisms.<ref name="odo1">{{cite journal  |vauthors=Odom DT, Zizlsperger N, Gordon DB, etal |title=Control of pancreas and liver gene expression by HNF transcription factors |journal=Science |volume=303 |issue=5662 |pages=1378–81 |date=February 2004 |pmid=14988562 |pmc=3012624 |doi=10.1126/science.1089769 |bibcode=2004Sci...303.1378O }}</ref><ref name="boy1">{{cite journal  |vauthors=Boyer LA, Lee TI, Cole MF, etal |title=Core transcriptional regulatory circuitry in human embryonic stem cells |journal=Cell |volume=122 |issue=6 |pages=947–56 |date=September 2005 |pmid=16153702 |pmc=3006442 |doi=10.1016/j.cell.2005.08.020 }}</ref><ref name="ira1">{{cite journal |vauthors=Iranfar N, Fuller D, Loomis WF |title=Transcriptional regulation of post-aggregation genes in Dictyostelium by a feed-forward loop involving GBF and LagC |journal=Dev. Biol. |volume=290 |issue=2 |pages=460–9 |date=February 2006 |pmid=16386729 |doi=10.1016/j.ydbio.2005.11.035 |doi-access=free }}</ref> A distinct set of network motifs were identified in other types of biological networks such as neuronal networks and protein interaction networks.<ref name="mil2" /><ref name="maa1">{{cite journal  |vauthors=Ma'ayan A, Jenkins SL, Neves S, etal |title=Formation of regulatory patterns during signal propagation in a Mammalian cellular network |journal=Science |volume=309 |issue=5737 |pages=1078–83 |date=August 2005 |pmid=16099987 |pmc=3032439 |doi=10.1126/science.1108876 |bibcode=2005Sci...309.1078M }}</ref><ref name="pta1">{{cite journal  |vauthors=Ptacek J, Devgan G, Michaud G, etal |title=Global analysis of protein phosphorylation in yeast |journal=Nature |volume=438 |issue=7068 |pages=679–84 |date=December 2005 |pmid=16319894 |doi=10.1038/nature04187|bibcode=2005Natur.438..679P |url=https://authors.library.caltech.edu/56271/2/Tables.pdf |type=Submitted manuscript }}</ref>
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生物学研究试图解释为生物网络检测到的模体。例如,在接下来的工作中,文献[17]在大肠杆菌中发现的网络模体存在于其他细菌<ref name="eic1">{{cite journal  |vauthors=Eichenberger P, Fujita M, Jensen ST, etal |title=The program of gene transcription for a single differentiating cell type during sporulation in ''Bacillus subtilis'' |journal=PLOS Biology |volume=2 |issue=10 |pages=e328 |date=October 2004 |pmid=15383836 |pmc=517825 |doi=10.1371/journal.pbio.0020328 }} {{open access}}</ref>以及酵母<ref name="mil3">{{cite journal |vauthors=Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U |title=Network motifs: simple building blocks of complex networks |journal=Science |volume=298 |issue=5594 |pages=824–7 |date=October 2002 |doi=10.1126/science.298.5594.824 |pmid=12399590|bibcode=2002Sci...298..824M |citeseerx=10.1.1.225.8750 }}</ref><ref name="lee1">{{cite journal  |vauthors=Lee TI, Rinaldi NJ, Robert F, etal |title=Transcriptional regulatory networks in Saccharomyces cerevisiae |journal=Science |volume=298 |issue=5594 |pages=799–804 |date=October 2002 |pmid=12399584 |doi=10.1126/science.1075090 |bibcode=2002Sci...298..799L }}</ref>和高等生物的转录网络中。文献<ref name="odo1">{{cite journal  |vauthors=Odom DT, Zizlsperger N, Gordon DB, etal |title=Control of pancreas and liver gene expression by HNF transcription factors |journal=Science |volume=303 |issue=5662 |pages=1378–81 |date=February 2004 |pmid=14988562 |pmc=3012624 |doi=10.1126/science.1089769 |bibcode=2004Sci...303.1378O }}</ref><ref name="boy1">{{cite journal  |vauthors=Boyer LA, Lee TI, Cole MF, etal |title=Core transcriptional regulatory circuitry in human embryonic stem cells |journal=Cell |volume=122 |issue=6 |pages=947–56 |date=September 2005 |pmid=16153702 |pmc=3006442 |doi=10.1016/j.cell.2005.08.020 }}</ref><ref name="ira1">{{cite journal |vauthors=Iranfar N, Fuller D, Loomis WF |title=Transcriptional regulation of post-aggregation genes in Dictyostelium by a feed-forward loop involving GBF and LagC |journal=Dev. Biol. |volume=290 |issue=2 |pages=460–9 |date=February 2006 |pmid=16386729 |doi=10.1016/j.ydbio.2005.11.035 |doi-access=free }}</ref>在其他类型的生物网络中发现了一组不同的网络模体,如神经元网络和蛋白质相互作用网络。<ref name="mil2" /><ref name="maa1">{{cite journal  |vauthors=Ma'ayan A, Jenkins SL, Neves S, etal |title=Formation of regulatory patterns during signal propagation in a Mammalian cellular network |journal=Science |volume=309 |issue=5737 |pages=1078–83 |date=August 2005 |pmid=16099987 |pmc=3032439 |doi=10.1126/science.1108876 |bibcode=2005Sci...309.1078M }}</ref><ref name="pta1">{{cite journal  |vauthors=Ptacek J, Devgan G, Michaud G, etal |title=Global analysis of protein phosphorylation in yeast |journal=Nature |volume=438 |issue=7068 |pages=679–84 |date=December 2005 |pmid=16319894 |doi=10.1038/nature04187|bibcode=2005Natur.438..679P |url=https://authors.library.caltech.edu/56271/2/Tables.pdf |type=Submitted manuscript }}</ref>
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The computational research has focused on improving existing motif detection tools to assist the biological investigations and allow larger networks to be analyzed. Several different algorithms have been provided so far, which are elaborated in the next section in chronological order.
 
The computational research has focused on improving existing motif detection tools to assist the biological investigations and allow larger networks to be analyzed. Several different algorithms have been provided so far, which are elaborated in the next section in chronological order.
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另一方面,对于计算研究的重点则是改进现有的模体检测工具,以协助生物学研究,并允许对更大的网络进行分析。到目前为止,已经提供了几种不同的算法,这些算法将在下一节按时间顺序进行阐述。
    
Most recently, the acc-MOTIF tool to detect network motifs was released.<ref>{{Cite web | url=http://www.ft.unicamp.br/docentes/meira/accmotifs/ |title = Acc-Motif: Accelerated Motif Detection}}</ref>
 
Most recently, the acc-MOTIF tool to detect network motifs was released.<ref>{{Cite web | url=http://www.ft.unicamp.br/docentes/meira/accmotifs/ |title = Acc-Motif: Accelerated Motif Detection}}</ref>
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最近,还发布了用于检测网络基序的acc基序工具。<ref>{{Cite web | url=http://www.ft.unicamp.br/docentes/meira/accmotifs/ |title = Acc-Motif: Accelerated Motif Detection}}</ref>
    
==Motif discovery algorithms==
 
==Motif discovery algorithms==
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