ltr retrotransposons exist in all eukaryotic genomes ( 14 ) and are especially widespread in plants . they have been found to be the main components of large plant genomes ( 58 ) . dynamics of these elements are now regarded as an important force in genome and gene evolution . for example , their amplification and removal shape the organization and change the size of genomes ( 9,10 ) ; their transposition effects gene expression ( 11 ) ; and cases of gene movement via ltr retrotransposons were also reported recently ( 12 ) . high throughput technologies for dna sequencing are providing unprecedented chance to explore their functions and evolutionary impact on the basis of large - scale genetic information ( 1316 ) . it is urgent to develop efficient tools for locating these elements in rapidly deposited genomic sequences . to date , most widely adopted methods of ltr retrotransposon identification in dna sequences are based on alignment of known elements database to target genome . this class of methods can well detect elements in the database , but can hardly discover elements that is far related to or not in the database . on the other hand , analysis of many sequences of ltr elements in nearly 20 years revealed some structural features ( signals ) common in these elements , including long terminal repeats ( ltrs ) , target site repeats ( tsrs ) , primer binding sites ( pbss ) , polypurine tract ( ppt ) and tg  ca box , as well as sites of reverse transcriptase ( rt ) , integrase ( in ) and rnaseh ( rh ) . however , tools for ab initio detection of ltr retrotransposons are still very limited : to the best of our knowledge , only two programs , ltr_struc ( 17 ) and ltr_par ( 18 ) , have been reported , none of them being a web server . we present here ltr_finder , a web server for efficient discovery of full - length ltr elements in large - scale dna sequences . considering the relationship between neighboring exactly matched sequence pairs , ltr_finder applies rapid algorithms to construct reliable ltrs and to predict accurate element boundaries through a multi - refinement process . furthermore , it detects important enzyme domains to improve the confidence of predictions for autonomous elements . ltr_finder accepts dna sequences file of fasta or multi - fasta format . only the first ungapped string in the description line is recorded to identify the input sequence , and the rest of descriptions are ignored . in the sequence lines , only a , c , g , t and sequence box , or upload a local file in the  file upload   box . the size of web uploading file should not exceed 50 mb . for users who need to scan very large size sequences , binary codes are available on request . when submitting a job because they are relatively conserved across organisms , trnas of a close related species can be used if those of the target species are not available . since pbs is critical in deciding 3boundaries of 5ltrs , omitting this parameter will probably cause missing prediction . occurrence of these sites adds weight of a candidate model to be a true autonomous element . if users choose domains in extension cutoff controls if two neighboring exactly matched pairs should be joined into a longer one , that is , the regions covering them is regarded as a longer highly similar pair .  reliable extension effects on identification of obscure overlapping elements . full - output shows details of predictions , including ltrs sizes , element locations in the input sequence , similarity of two ltrs , sharpness ( an index for boundary prediction reliability of ltr regions ) and so on . summary - output is extracted from full - output by omitting some detailed information . for each sequence the diagrams are convenient for human inspection and are very useful when analyzing potential overlapping elements : one can view the relative positions of signals inside ltr elements in details . in a diagram , two background colors , silver and white , are used to show sizes of objects . the program draws l pixels to represent l bases on the silver background while draws nlog(l ) pixels to represent l bases on the white background , where n is a constant controlling overall size of the diagram . if users fill in the  get result by e - mail box with a valid email address , the server will send the result instead of displaying it . ltr_finder accepts dna sequences file of fasta or multi - fasta format . only the first ungapped string in the description line is recorded to identify the input sequence , and the rest of descriptions are ignored . in the sequence lines , only a , c , g , t and sequence box , or upload a local file in the  file upload   box . the size of web uploading file should not exceed 50 mb . for users who need to scan very large size sequences , binary codes are available on request . when submitting a job because they are relatively conserved across organisms , trnas of a close related species can be used if those of the target species are not available . since pbs is critical in deciding 3boundaries of 5ltrs , omitting this parameter will probably cause missing prediction . occurrence of these sites adds weight of a candidate model to be a true autonomous element . if users choose domains in extension cutoff controls if two neighboring exactly matched pairs should be joined into a longer one , that is , the regions covering them is regarded as a longer highly similar pair .  reliable extension effects on identification of obscure overlapping elements . full - output shows details of predictions , including ltrs sizes , element locations in the input sequence , similarity of two ltrs , sharpness ( an index for boundary prediction reliability of ltr regions ) and so on . summary - output is extracted from full - output by omitting some detailed information . for each sequence the diagrams are convenient for human inspection and are very useful when analyzing potential overlapping elements : one can view the relative positions of signals inside ltr elements in details . in a diagram , two background colors , silver and white , are used to show sizes of objects . the program draws l pixels to represent l bases on the silver background while draws nlog(l ) pixels to represent l bases on the white background , where n is a constant controlling overall size of the diagram . if users fill in the  get result by e - mail box with a valid email address , the server will send the result instead of displaying it . we describe an example of running ltr_finder on yeast chromosome 10 to show the usage of the server . upload the sequence file , which can be obtained from saccharomyces genome database ( http://www.yeastgenome.org/ ) . here we use the version released on july 27 , 1997 in order to compare the results with that described in ( 19 ) , in which a standard benchmark of 50 full - length ltr retrotransposons on 16 yeast chromosomes were given . using the default parameters , choosing  saccharomyces cerevisiae trna database and  output with figure figure 1 gives a complete description of element 1 ( pictures of the same element 1 appear in figures 2 and 3 ) . explanation of the output items is given in the caption of figure 1 and more information on output format can be found in documents on the webpage . yeast chromosome x contains a region where two tandem elements resulted from recombination . the program reports two sets of rts and ins indicating the tandem structure ( figure 2 , elements 2 ) . a more sensitive search for overlapping elements by resetting reliable extension and  sharpness lower threshold parameters reports the inserted ltr ( figure 3 , element 3 ) . compared with the benchmark , locations of all elements status is an 11 bits binary string with each position indicating the occurrence of a certain signal . positions are as follows :   tg in 5end of 5ltr ;   ca in 3end of 5ltr ;   tg in 5end of 3ltr ;   ca in 3end of 3ltr ;   tsr ;   pbs ;   ppt ;   rt ;   in(core ) ;   in(c - term ) and   rh . element 2 is composed of two tandem ltr retrotransposons , which resulted from recombined insertion of a circular element . two sets of enzyme domains are detected . reliable extension to 0.95 and  sharpness lower threshold to 0.2 , the inserted element ( element 3 ) , its 5ltr locating at 477837478072 , is reported . status is an 11 bits binary string with each position indicating the occurrence of a certain signal . positions are as follows :   tg in 5end of 5ltr ;   ca in 3end of 5ltr ;   tg in 5end of 3ltr ;   ca in 3end of 3ltr ;   tsr ;   pbs ;   ppt ;   rt ;   in(core ) ;   in(c - term ) and   rh . element 2 is composed of two tandem ltr retrotransposons , which resulted from recombined insertion of a circular element . two sets of enzyme domains are detected . reliable extension to 0.95 and  sharpness lower threshold to 0.2 , the inserted element ( element 3 ) , its 5ltr locating at 477837478072 , is reported . using the whole genome of yeast ( 12  mb ) as input , the web server implemented on a 600mhz pc took only 30  s , with ram consumption < 18  m. a total of 52 models were detected and all the 50 target elements were found . among the test set , 48 were identified exactly , the remaining two predicted ones containing the targets with only 7  bp and 18  bp more in the 5ltrs , respectively . the testing results gave no false negative and only two false positive reports , showing high speed , high sensitivity ( 100% ) and specificity ( 96% ) . ltr_finder identifies full - length ltr element models in genomic sequence in four main steps . ltr_finder searches for all exactly matched string pairs in the input sequence by a linear time suffix - array algorithm ( 20 ) . each pair , say a , is composed of two identical members : string located upstream ( a5 ) and downstream ( a3 ) . here then it selects pairs of which distances between a5 and a3 as well as the overall sizes satisfy given restrictions . for each pair a and its downstream neighbor b , if the order of their locations in input sequence is 5 a5  b5  a3 b3 3 , the regions [ a5,b5 ] and [ a3,b3 ] will be checked whether they should be regarded as a longer highly similar pair . here highly similar means that similarity between two members of the merged pair is greater than calculation of the similarity involves in a global alignment of two regions : that inside two neighboring upstream strings and that inside two downstream strings . the pair keeps on extending until similarity between its members becomes less than  extension cutoff. then it is recorded as an ltr candidate for further analysis . after that , smith waterman algorithm is used to adjust the near - end regions of ltr candidates to get alignment boundaries . these boundaries are subject to re - adjustment again by tg  ca box and tsr supporting . at the end of this step , a set of regions in the input sequence secondly , ltr_finder tries to find signals in near - ltr regions inside these loci . the program detects pbs by aligning these regions to the 3tail of trnas and ppt by counting purines in a 15  bp sliding window along these regions . the program locates the most widely shared domain , rt , by first searching for its seven conserved subdomains , then chaining them together under distance restrictions using dynamic programming . this strategy is implemented to all six orfs and is capable to detect rt domain even when there is a frame shift . for other protein domains such as in and rh , it calls ps_scan ( 21 ) to find their locations and possible orfs . at last , the program gathers information and reports possible ltr retrotransposon models at different confidence levels according to how many signals and domains they hit . ltr_finder is the first web server devoted specially to full - length ltr retrotransposon discovery . it processes large - scale genomic sequences efficiently , which makes it applicable to rapid analysis of large genomes such as that of maize and wheat . a few improvements of the server are under way : ( i ) to make the interface more user - friendly , we plan to add buttons for automatic retrieval of sequences from genebank , embl and ddbj by accession number to facilitate user input . ( ii ) ltr elements close to functional units ( e.g. trnas , genes or centermeres ) will be reported specially . the graphic output of the vicinity of ltr elements will be enhanced to reflect the local organization of functional units and ltr elements . ( iii ) it is also known that ltr elements may insert into internal regions of other elements to form nested structure .
long terminal repeat retrotransposons ( ltr elements ) are ubiquitous eukaryotic transposable elements . 
 they play important roles in the evolution of genes and genomes . ever - growing amount of genomic sequences of many organisms present a great challenge to fast identifying them . 
 that is the first and indispensable step to study their structure , distribution , functions and other biological impacts . 
 however , until today , tools for efficient ltr retrotransposon discovery are very limited . 
 thus , we developed ltr_finder web server . given dna sequences , it predicts locations and structure of full - length ltr retrotransposons accurately by considering common structural features . 
 ltr_finder is a system capable of scanning large - scale sequences rapidly and the first web server for ab initio ltr retrotransposon finding . 
 we illustrate its usage and performance on the genome of saccharomyces cerevisiae . 
 the web server is freely accessible at http://tlife.fudan.edu.cn / ltr_finder/.