various large - scale and high - throughput techniques , such as chromosome banding ( 1,3 ) , comparative genomic hybridization ( cgh ) ( 4 ) and fluorescence in situ hybridization ( fish ) ( 5 ) , are being used in modern cancer cytogenetics to detect structural and copy number changes in chromosomes .
the most common type of mutation among the known cancer genes is chromosomal translocation ( 6 ) .
it can deregulate the gene expression by disrupting the promoter region of the gene or by joining the gene with enhancer elements like immunoglobulin or t - cell receptor genes ( 7 ) .
alternatively , fusion of two coding regions creates a chimeric gene that encodes a fusion protein that interferes with the normal regulating pathways ( 2,8 ) .
abl , the target protein of the drug gleevec treating chronic myeloid leukemia ( cml ) ( 8,9 ) .
cml is associated in most cases with a chromosomal translocation between chromosomes 9 and 22 that creates the philadelphia chromosome .
the bcr gene in chr22 is fused with the gene abl in chr9 , so called the t(9;22)(q34;q11 ) translocation .
the tyrosine kinase activity of abl is constantly activated by the bcr gene ( gtpase activator ) in the fusion protein , resulting in the rapid cellular mitosis and inability of the cell to perform apoptosis .
two adjacent , independent genes may be co - transcribed and the intergenic region is spliced out so that the resulting fused transcript possesses exons from both genes ( 10 ) .
this phenomenon , termed as cotranscription and intergenic splicing ( cotis ) , can lead to fusion protein or altered promoter region for the downstream gene in the same way as chromosome translocation .
furthermore , trans - splicing can join two independently transcribed mrna sequences at canonical exon 
even though several cases of natural trans - splicing are reported in human ( 11,12 ) , it is generally considered to be rare and will be ignored in this work . given the importance of chromosome aberration in cancer detection , prognosis and target identification , it is quite natural to search for chimeric sequences in the genbank .
alterbi and co - workers ( 13 ) developed a screening procedure to identify heterologous , spliced mrnas with potential origin from chromosomal translocation , mrna trans - splicing and multi - locus transcription .
hahn et al . ( 14 ) extended this approach to include expressed sequence tag ( est ) sequences that expanded the search scope significantly .
ncbi 's database of cancer chromosomes ( 15 ) integrated the nci / ncbi sky / m - fish and cgh database and the nci mitelman database of chromosome aberrations in cancers .
the cancer genome project at the sanger institute maintains a list of cancer genes based on published scientific literatures ( 6 ) .
mutation data and associated information for these cancer genes are stored in the cosmic database ( 16 ) .
atlas of genetics and cytogenetics in oncology and haematology is a peer - reviewed resource that contains concise and updated cards on genes involved in cancer , cytogenetics and clinical entities in oncology , and cancer - prone diseases ( 17 ) . in this paper , we describe a new database of fusion genes , chimerdb .
it aims to be a knowledgebase that integrates bioinformatics analysis of transcript sequences ( mrna and est ) , literature data from scientific journals ( 6 ) and omim data on translocation ( 18 ) .
all mrna and est sequences in the genbank ( release 148 ; june 15 , 2005 ) were aligned onto the human genome ( ncbi build 35 ) using the blat program ( 19 ) .
minimum length and percent identity of valid alignments were 100 bp and 93% , respectively .
small overlap ( < 10 bp ) was allowed due to uncertainty in blat alignments .
alignments in the same chromosome were restricted to be in opposite orientation to avoid fusion by cotis .
we found 261 mrna and 2484 est sequences as fusion candidates , including artificial chimeras created by accidental ligation of different cdnas during the cloning procedure .
fusion points in true chimeras usually coincide with a splice site since chromosome breakage tends to take place in long intronic regions rather than in short exons ( 14 ) . allowing 10 bp deviation from known splice sites
fusion cases owing to cotis can be identified using the ecgene clustering system ( 20,21 ) .
ecgene clusters sequences that share any splice sites in the genomic alignment , taking gene orientation into consideration .
fusion transcripts cause two neighboring genes to join to form a single cluster in the ecgene system .
therefore , we searched for ecgene clusters ( version 1.2 ) that contained two non - overlapping known genes and identified fusion transcripts .
fusion by cotis creates a subtle problem in the genome - based est clustering procedure that groups sequences sharing any splice sites .
we also imported the list of cancer genes associated with chromosome translocation from the cancer genome project at the sanger institute ( 6 ) .
current cancer gene census contains 257 translocation cases involving 346 genes , most of which coincide with our pubmed search result .
literature databases should greatly extend the utility of fusion database by providing literature proof and relevant medical information for each computationally identified event .
one of the major problems in dealing with heterogeneous databases , especially the literature data , is the use of aliases for the same gene .
alias field in entrez gene database ( 22 ) was used to deal with different names for the same gene . in silico results from transcript mapping , literature and
furthermore , mitelman 's recurrent aberration database and the atlas chromosomes in cancer data were also integrated into chimerdb .
currently , chimerdb contains 1258 fusion cases that involve 1777 genes , 381 mrna and 654 est sequences . assuming total number of human genes 25 
000 , this implies that 4.4% of human genes are involved in chromosome translocation and another 2.7% of human genes show fusion between neighboring genes ( cotis ) .
it should be noted that overlap between the transcript mapping data and other known databases is not large .
this suggests that majority of known chromosome translocations are not supported by transcript data , such as mrna and est .
unless transcripts were discarded owing to low alignment quality , they would be from non - sequence - based methods and it would be interesting to obtain clone - based sequence data for those cases .
all mrna and est sequences in the genbank ( release 148 ; june 15 , 2005 ) were aligned onto the human genome ( ncbi build 35 ) using the blat program ( 19 ) .
minimum length and percent identity of valid alignments were 100 bp and 93% , respectively .
small overlap ( < 10 bp ) was allowed due to uncertainty in blat alignments .
alignments in the same chromosome were restricted to be in opposite orientation to avoid fusion by cotis .
we found 261 mrna and 2484 est sequences as fusion candidates , including artificial chimeras created by accidental ligation of different cdnas during the cloning procedure .
fusion points in true chimeras usually coincide with a splice site since chromosome breakage tends to take place in long intronic regions rather than in short exons ( 14 ) . allowing 10 bp deviation from known splice sites
fusion cases owing to cotis can be identified using the ecgene clustering system ( 20,21 ) .
ecgene clusters sequences that share any splice sites in the genomic alignment , taking gene orientation into consideration .
fusion transcripts cause two neighboring genes to join to form a single cluster in the ecgene system .
therefore , we searched for ecgene clusters ( version 1.2 ) that contained two non - overlapping known genes and identified fusion transcripts .
fusion by cotis creates a subtle problem in the genome - based est clustering procedure that groups sequences sharing any splice sites .
we also imported the list of cancer genes associated with chromosome translocation from the cancer genome project at the sanger institute ( 6 ) .
current cancer gene census contains 257 translocation cases involving 346 genes , most of which coincide with our pubmed search result .
literature databases should greatly extend the utility of fusion database by providing literature proof and relevant medical information for each computationally identified event .
one of the major problems in dealing with heterogeneous databases , especially the literature data , is the use of aliases for the same gene .
all records use the official hugo gene to avoid this problem . alias field in entrez gene database ( 22 )
was used to deal with different names for the same gene . in silico results from transcript mapping , literature and
furthermore , mitelman 's recurrent aberration database and the atlas chromosomes in cancer data were also integrated into chimerdb .
currently , chimerdb contains 1258 fusion cases that involve 1777 genes , 381 mrna and 654 est sequences . assuming total number of human genes 25 
000 , this implies that 4.4% of human genes are involved in chromosome translocation and another 2.7% of human genes show fusion between neighboring genes ( cotis ) . it should be noted that overlap between the transcript mapping data and other known databases is not large
this suggests that majority of known chromosome translocations are not supported by transcript data , such as mrna and est .
unless transcripts were discarded owing to low alignment quality , they would be from non - sequence - based methods and it would be interesting to obtain clone - based sequence data for those cases .
the contents of chimerdb can be accessed at . it supports various types of queries such as gene name and cytogenetic band position .
query can be a breakpoint ( e.g. aml1 ) or a fusion event ( e.g. bcr
details page opens an output page for a specific fusion case that consists of a summary table , detailed information table and fusion transcript table as shown in figure 1a .
it includes extensive links to relevant resources , such as the entrez gene , omim and pubmed databases .
links to ncbi cancer chromosomes provide detailed information on sky / m - fish and cgh and mitelman databases  primary databases for cancer cytogenetics .
links to atlas of genetics and cytogenetics in oncology and haematology database allow access to community efforts to annotate cancer genes , rich in cytogenetic and clinical information .
transcript direction , aligned region , number of exons , deviation of fusion boundary from known splice site and so on .
intact and affected domains before and after translocation are also summarized using the interpro database ( 23 ) .
figure 1b is the custom genome browser showing alignment of fusion transcripts in each gene .
most fusion genes owing to cotis do not have detailed information on their functional significance yet .
therefore , we simply provide the minimal information  fused genes , genomic locus , functional domains , alignment browser and exon / intron properties .
chimerdb is an integrated database for fusion sequences that includes bioinformatics analysis , literature data and omim data .
however , functional significance of fusion events should be examined thoroughly so that these fusion events could serve as drug targets for cancer treatment .
expression analysis of fused transcripts in different histological and pathological conditions should be performed with the bioinformatics analysis such as domain and promoter changes , frame shift and so on .
integrative approach that combines high - throughput techniques , such as sky , cgh , snp chip , microarray , proteomics , interactions and pathway analysis , would prove to be powerful in elucidating the functional significance of fusion genes .
 chromosome translocation and gene fusion are frequent events in the human genome and are often the cause of many types of tumor . 
 chimerdb is the database of fusion sequences encompassing bioinformatics analysis of mrna and expressed sequence tag ( est ) sequences in the genbank , manual collection of literature data and integration with other known database such as omim . 
 our bioinformatics analysis identifies the fusion transcripts that have non - overlapping alignments at multiple genomic loci . 
 fusion events at exon  exon borders are selected to filter out the cloning artifacts in cdna library preparation . 
 the result is classified into two groups  genuine chromosome translocation and fusion between neighboring genes owing to intergenic splicing . 
 we also integrated manually collected literature and omim data for chromosome translocation as an aid to assess the validity of each fusion event . 
 the database is available at   for human , mouse and rat genomes . 
INTRODUCTION
DATABASE CONSTRUCTION
None
Literature database
Database integration
WEB INTERFACE
FUTURE DIRECTIONS
Figures and Tables