document: schistosomatidae ( platyhelminthes : digenea ) includes several digenetic endoparasites with complex life cycles , whose developmental stages alternate between intermediate ( freshwater gastropods ) and definitive hosts ( birds , reptiles , fishes , and mammals ) . 
   another important feature is the increased longevity ( over 5 years ) of the schistosoma species in the human host . 
   schistosoma , the avian and mammalian blood flukes , is the best studied genus of schistosomatidae . 
   several species are described , six of which infect humans causing schistosomiasis : s. haematobium , s. intercalatum , s. japonicum , s. malayensis , s. mansoni , and s. mekongi . 
   other species are known to infect a broad range of mammals such as hippopotamus , rodents , carnivores , and ruminant animals like buffalo , cattle , goat , lechwe , and sheep . 
   for example , s. mattheei , more commonly found in cattle , is believed to form hybrids between s. mattheei and s. haematobium thus increasing its snail and definitive host range . 
   schistosomiasis , a chronic and debilitating disease , is considered by the world health organization as one of the most serious public health issues and the second most prevalent tropical disease with high morbidity in the world . 
   schistosomiasis is endemic in 77 countries   and its transmission is dependent on the existence and distribution of intermediate hosts . 
   it is estimated that 237 million people require treatment worldwide and that 600 to 779 million people live in endemic areas , under infection risk . yet , exacerbating this scenario , this disease is responsible for the loss of 1.7 to 4.5 millions of years of life in the world , measured by disability - adjusted life years ( daly ) , one of the highest indexes among all the neglected tropical diseases . 
   control of schistosomiasis represents a great challenge and it is based on drug treatment ( praziquantel ) , snail control , improved sanitation , and health education . 
   the development of powerful and scalable methods to analyse nucleic acids and proteins has changed the way biological data is surveyed . 
   the application of such technologies , together with the development of powerful computational tools and methods , have expanded our perspective of schistosome biology and allowed a better understanding of processes such as host - parasite interaction [ 810 ] . 
   this paper aims to discuss some advances in schistosome research with emphasis on genomics and transcriptomics . 
   first , we summarize the current status of sequencing projects of nuclear and mitochondrial genomes . 
   then , we present key findings in transcriptomic analyses . finally , we point out the main challenges of the current research and suggest some future directions in schistosoma genomic and transcriptomic studies . 
   in order to strengthen traditional methods and provide new information to improve success towards schistosomiasis control , the scientific community joined efforts to assess the schistosoma genomic information , starting in 1994 , as an initiative of who / tdr ( unicef - undp - world bank - who special programme for research and training in tropical diseases ) [ 11 , 12 ] . at that time , 
   only a few hundred expressed sequence tags ( ests ) from s. mansoni were available . 
   the who / tdr support opened the possibility to generate data that could be translated into new tools for schistosomiasis diagnostics and treatment , representing the  kickoff  of schistosoma nuclear genome studies . 
   the karyotype of known schistosoma species comprises seven pairs of autosomes and one pair of sex chromosomes ( female = zw , male = zz ) , ranging in size from 18 to 73 megabases ( mb ) [ 14 , 15 ] . 
   the s. japonicum ( anhui isolate ) and s. mansoni ( puerto rico isolate ) genomes were decoded and simultaneously published as an initiative of the wellcome trust sanger center institute in collaboration with the institute for genomic research ( tigr ) and the schistosoma japonicum genome sequencing and functional analysis consortium [ 16 , 17 ] . recently 
   , the s. haematobium ( egyptian isolate ) genome was sequenced opening new possibilities in comparative genomics of schistosomes . 
   s. haematobium , s. japonicum , and s. mansoni carry a nuclear genome of 385 , 397 , and 363 mb composed by approximately , 13,073 , 13,469 , and 10,852 protein - coding genes , respectively [ 1619 ] . 
   it is worth to mention that the number of predicted protein - coding genes does not reflect the genome structure per se , but the actual state of analyses of the different draft genome data . 
   the genetic linkage map of s. mansoni was obtained and allowed the refinement of the genome sequencing data providing a means for gene discovery and gene function analysis [ 20 , 21 ] . 
   more importantly , it has allowed the identification of genetic loci that determine important traits such as host specificity , virulence , and drug resistance . 
   in fact , although the quality and annotation of the s. mansoni genome sequence data have been greatly improved ( see below ) ; the corresponding data of s. haematobium and s. japonicum are still considered drafts [ 1619 ] . 
   their genome sequences are distributed in a large number of contigs ; therefore extensive work is required . 
   constant data refinement is necessary to provide a reliable comprehension of the genome and gene models and to provide a curated annotation . 
   such strategies include new assembly of existing capillary reads supplemented with an additional ~90,000 fosmid and bac end sequences , deep sequencing of clonal dna ( nmri strain , puerto rican origin ) using 108-based paired reads on illumina genome analyzer iix platform , and rna - seq data of different parasite life stages . 
   progress on the knowledge of s. mansoni genome features is still expanding , especially with the application of the next - generation sequencing platforms and single nucleotide polymorphism typing methods . 
   for instance , 14 new microsatellite markers were recently identified by de novo assembly of massive sequencing reads ; these new features can be employed for pedigree studies . yet , newer sequencing technologies will allow for the development of population genomics studies of field , laboratory , and clinical isolates . as a result of the availability of the schistosoma genome sequence data , comparative analyses across different species became possible bringing together different areas of research [ 21 , 23 , 24 ] . 
   comparative genomics of three schistosoma species revealed several conserved features such as the overall gc content , sequence identity , presence of repetitive elements , and synteny . 
   this genome - wide analysis corroborates previous genetic studies and supports the evolutionary hypothesis of s. haematobium and s. mansoni as the most related species , followed by s. japonicum , to the exclusion of other trematoda such as clonorchis , fasciola , and schmidtea . 
   mitochondrial genes have been used as molecular markers for species and strain identification , which is key to a variety of studies such as phylogenetics , population genetics , biogeography , and molecular ecology [ 2529 ] . besides helping to elucidate the evolutionary relationships among taxa 
   , mitochondrial genes have been successfully applied into epidemiological studies , monitoring , and control of microbes , parasites , and vectors of medical and socioeconomic importance . 
   the analysis of the whole mitochondrial genome of diverse taxa has changed the perspective of such studies . 
   the mitochondrial genome of six schistosoma species was sequenced ( table 1 ) including s. haematobium ( nc_008074 ) , s. japonicum ( nc_002544 ) , s. mansoni ( nc_002545 ) , s. malayensis , s. mekongi ( nc_002529 ) , and s. spindale ( nc_008067 ) [ 27 , 3032 ] . 
   these genomes range in size from 13,503 to 16,901  bp and encode 36 genes comprising two ribosomal genes ( large and small subunit rrna genes ) , and 22 transfer rna ( trna ) genes , as well as 12 protein - encoding genes ( atp6 , cob , cox13 , nad16 , and nad4l ) . 
   the atp8 gene , commonly found in other phyla , is absent from platyhelminthes , whose mitochondrial genomes have been analysed . moreover 
   , each schistosoma mitochondrial genome contains a long noncoding region that is divided into two parts by one or more trna genes , which is found in other platyhelminthes and vary in length according to each taxon . 
   comparative mitogenomics have revealed a highly conserved gene order among distinct platyhelminthes with the exception of some schistosoma species [ 25 , 3033 ] . 
   the mitochondrial genome of the asian schistosomes , s. japonicum and s. mekongi , displays the same gene order as other digenea and cestoda [ 25 , 32 ] . in contrast , the gene order in the mitochondrial genome of s. haematobium , s. mansoni , and s. spindale is strikingly different from other taxa [ 25 , 30 ] . 
   the unique gene order rearrangements identified in these species constitute valuable information to the reconstruction of the phylogenetic relationships of schistosoma and other platyhelminthes ( section 3.1 ) . 
   the use of genomic data is valuable to the understanding of the evolutionary history of schistosoma especially due to the absence of fossil records . 
   molecular markers have been used to test hypotheses in a variety of schistosoma phylogenetic , phylogeographic and epidemiological studies [ 4 , 25 , 3436 ] . 
   traditionally , these markers include the nuclear ribosomal rna genes ( 18s , 5.8s , and 28s ) and the internally transcribed spacer ( its ) region besides a number of mitochondrial genes ( cob , cox13 , nad16 , etc . ) . 
   based on mitochondrial data from different studies , a standard phylogeny of 23 schistosoma species was proposed . 
   these clades include ( 1 ) the s. japonicum complex ( s. japonicum , s. malayensis , s. mekongi , s. ovuncatum , and s. sinensium ) found in central and south eastern asia ; ( 2 ) the s. hippopotami clade ( s. edwardiense and s. hippopotami ) distributed in africa ; ( 3 ) the proto - s . 
   mansoni clade ( s. incognitum and s. turkestanicum ) in central asia , near east , and eastern europe ; 
   ( 4 ) the s. mansoni clade ( s. mansoni and s. rodhaini ) found in africa and south america ; ( 5 ) the s. haematobium clade ( s. bovis , s. curassoni , s. guineensis , s. haematobium , s. intercalatum , s. kisumuensis , s. leiperi , s. margrebowiei , and s. mattheei ) occurring in different parts of africa ; ( 6 ) the s. indicum clade ( s. indicum , s. nasale , and s. spindale ) found in india and south asia . 
   there are divergent opinions concerning the origin of the genus schistosoma and its intermediate snail host [ 25 , 3739 ] . 
   the  out of asia  hypothesis is the most generally accepted , indicating a migration followed by dispersion of these parasites from asia to africa . in this regard , studies of molecular phylogeny suggested that the genus schistosoma had its origin in asia and ( at least two descendants ) colonized the african continent independently , where they easily radiated , becoming exclusive parasites of planorbid snails . returning to asia , the parasites diversified into groups of species , characterized by the position of the spike in the eggs . 
   the molecular phylogeny of seven schistosoma species suggested that schistosomes were endoparasites of rodents and ruminants and were transmitted to the first hominids in africa as a migration to savanna areas occurred . 
   however , in order to better define the schistosoma origin , there is a need to sample a broader range of species . 
   most of the widely accepted schistosoma phylogenies are primarily based on sequence alignments of mitochondrial genes such as cox13 , and nad16 , [ 25 , 30 ] . 
   indeed , these gene rearrangements , considered to be rare evolutionary events , have been applied to an increasing number of studies ( cf . ) . 
   as mentioned before , major changes in the mitochondrial gene order were identified in some schistosoma species ( section 2.2 ) , more specifically in the african clades ( s. mansoni and s. haematobium ) and the s. indicum group ( s. spindale ) . 
   this provides further evidence for the asian ancestry of schistosomes and corroborates the concept of the reinvasion of asia by members of the s. indicum group from africa [ 27 , 30 ] . besides reconstructing the phylogenetic relationships of diverse taxa 
   , the evolutionary framework has been applied to improve functional annotation of genes and gene products , as well as to study gene / protein family evolution . 
   phylogenomics has allowed the identification and characterization of all eukaryotic protein kinases encoded in the s. mansoni genome and improved the functional annotation of over 40% of them , highlighting the molecular diversity of these enzymes [ 42 , 43 ] . 
   a phylogenetic analysis was also employed in the classification of s. mansoni histone proteins , which play a key role in epigenetic modifications that might reflect the parasite complex lifestyle . by applying an evolutionary framework to analyse a large sequence dataset from a broad range of organisms , functional annotation of the s. mansoni histone proteins 
   moreover , phylogenomics has unraveled the distinct evolutionary histories of three expanded endopeptidase families in s. mansoni . 
   this analysis included members of the metallopeptidase m8 , serine peptidase s1 , and aspartic peptidase a1 families , which were originated from successive events of gene duplication followed by divergence in the parasite lineage after its diversification from other metazoans . 
   other protein families such as nuclear receptors and antioxidants have been characterized in s. mansoni by applying evolutionary and functional approaches [ 46 , 47 ] . 
   the identification of smnr4a , a member of the nuclear receptor subfamily 4 , and its relatedness to the human homologs were corroborated by phylogenetic analysis . 
   thioredoxin and glutathione systems , involved in a variety of cellular processes including antioxidant defense , differ in parasitic and free - living platyhelminthes . by applying different phylogenetic methods and experimental testing 
   , it has been shown that the canonical enzymes of such systems were lost in the parasitic lineages . 
   the availability of sequencing data from mitochondrial genomes from closely related taxa to schistosoma has provided a basis for studies ranging from phylogenetic systematics to molecular ecology and so forth [ 27 , 29 , 48 , 49 ] . 
   importantly , it allowed the assessment of molecular markers prior to broad scale sampling by comparing data from individual genes versus completely sequenced mitochondrial genomes . 
   data from african and asian schistosomes were compared to an s. mansoni intraspecific dataset showing a positive correlation between polymorphism and species divergence . a positive correlation rather than random distribution 
   furthermore , partial sequences of cox1 have been shown not to be the ideal marker for either species identification or population studies of schistosoma species . instead , 
   authors have suggested the use of cox3 and nad5 sequences for both phylogenetic and population studies of such species . 
   dna barcoding was performed for samples of s. haematobium using cox1 and nad1 as molecular markers . 
   the results supported the identification of group 1 and 2 haplotypes based on phylogenetic analysis . 
   moreover , no change in genetic diversity was detected across samples collected over different time points . 
   this approach allowed the development of new assays based on group - specific pcr primers and snapshot probes to assist genetic screening of schistosome isolates . 
   another study employing mitochondrial sequences was performed in schistosoma cercariae harvested from biomphalaria choanomphala as part of parasitological and malacological surveys for s. mansoni across lake victoria . 
   dna barcoding of cercarial samples revealed the presence of hybrid species between s. mansoni and s. rodhaini , which is typically found in small mammals . 
   dna barcoding studies are underway for an increasing number of schistosoma species ( table 1 ) , whose data is made available through the barcode of life database ( bold ) system ( http://www.boldsystems.org/ ) . 
   this initiative includes contributors from the biodiversity institute of ontario , canada , and the university of new mexico , usa , among others . 
   other schistosomatidae genera are subject to dna barcoding analysis such as allobilharzia , austrobilharzia , bilharziella , bivitellobilharzia , dendritobilharzia , gigantobilharzia , griphobilharzia , heterobilharzia , macrobilharzia , orientobilharzia , ornithobilharzia , schistosomatium , and trichobilharzia . 
   advances in dna barcoding of a broader range of schistosomatidae will create a framework for species identification from environmental and clinical samples as well as specimens deposited in biological collections . 
   moreover , dna barcoding analysis will help reconstructing the evolutionary relationships across different platyhelminthes and ultimately improve our understanding of parasite biology and evolution . 
   transcriptomic analyses are valuable not only for studies of differential regulation in gene expression , but also for the identification of splicing variants . 
   these approaches have proved to be essential in the identification of gene - coding regions during the process of genome annotation . in this section 
   , we aim to review the achievements in schistosoma transcriptomic studies that range from the whole organism and tissue analyses to those performed at the cellular level . 
   transcriptomics in physiological conditions and in response to a variety of treatments are investigated with respect to the interaction with the host as well as other environments . 
   this section summarizes the accomplishments of gene function studies and the diverse techniques that are being employed . 
   a fine tuning in gene expression of parasites must occur to enable them to survive in such a complex and extremely diverse milieu , adapting to diverse environments as evading the immune system and , at the same time , exploiting different hosts . 
   transcriptomic studies came along allowing a temporal and quantitative analyses of gene expression , which are crucial to completely exploit different datasets and assess parasite biology at the molecular level . aiming to elucidate the differential regulation on the schistosoma transcriptomics , 
   a large number of projects employed diverse strategies , such as the ones using expressed sequence tags ( ests ) , open reading frame expressed sequence tags ( orestes ) , and serial analysis of gene expression ( sage ) [ 52 , 53 ] . 
   the increasing number of projects resulted in the production of a vast amount of sequence data and their availability in public databases . 
   it is noteworthy that only s. japonicum , s. mansoni and , not until very recently , s. haematobium had some of their transcriptome explored ( table 1 ) . 
   the large number of transcriptome projects accelerated the studies in this area by providing means to the use of complementary approaches , especially microarray analysis . 
   together , these approaches have been used to answer a wide range of questions . in the early years 
   , microarray datasets conceived the profile of gene expression between genders of schistosoma species such as s. japonicum and s. mansoni [ 5456 ] . 
   this greatly extended the number of known sex - associated genes and also provided new insights into changes in gene expression promoted by parasite pairing . 
   in addition , gender biased alternative splicing patterns were observed , which are perhaps involved in the generation and maintenance of the sexual dimorphism . 
   later , studies profiled the s. mansoni gene expression in different life stages broadening our understanding of factors controlling schistosome development [ 8 , 53 , 58 ] . while comparing different parasite life stages , 
   information acquired from microarray datasets highlighted putative antischistosome candidate molecules to be used as vaccine targets including dyp - type peroxidases , fucosyltransferases , g - protein coupled receptors , leishmanolysins , tetraspanins , and the netrin / netrin receptor complex . some of these candidates ( fucosyltransferases , leishmanolysins , and tetraspanins ) are members of protein families , which are expanded in the s. mansoni predicted proteome in comparison with other metazoans as inferred by phylogenomic analysis ( http://phylomedb.org/ ) . 
   leishmanolysins , which are members of the metallopeptidase m8 family , were analysed in detail corroborating the potential of these enzymes as future therapeutic targets . 
   another study identified upregulated genes during the first five days of schistosomula development in vitro that are involved in blood feeding , tegument and cytoskeletal development , cell adhesion , and stress responses . 
   the highly upregulated genes included a tegument tetraspanin sm - tsp-3 , a protein kinase , a novel serine protease and serine protease inhibitor , and intestinal proteases belonging to distinct mechanistic classes . 
   other groups have analysed immunity towards schistosoma using protein microarrays as a vaccine discovery tool . 
   they selected a subset of proteins from genomic , transcriptomic , and proteomic data to perform experimental validation aiming at identifying novel antischistosome vaccine candidates [ 60 , 61 ] . 
   recently , an elegant approach to investigate specific tissues such as gastrodermis and both genders reproductive tissues was performed by applying laser microdissection microscopy combined to microarray . 
   these studies brought the perspective of expediting tissue - specific profiling [ 62 , 63 ] . 
   additionally , expression profiles of s. japonicum were explored in studies comparing two chinese isolates ( anhui and zhejiang ) , as well as the anhui chinese and philippines isolates [ 55 , 64 ] . 
   later , an interspecies study compared the s. japonicum and s. mansoni transcriptomes . surprisingly , despite their large phenotypic differences , there was a reduced number of differentially expressed genes based on the expression profile , which might reflect a limitation of the technique ( preferential hybridization related to species polymorphisms ) . bypassing these pitfalls , 
   the next generation sequencing platforms allow exploiting expression data ( rna - seq ) of any organism without previous knowledge of the genome or transcriptome and , further , will reveal new features of the parasite transcriptional landscape . 
   the most recent achievement in this area was the refinement of the genomics and transcriptomics data using a combination of sanger capillary sequencing , next generation dna sequencing , genetic markers , and rna - seq data from several s. mansoni life stages . a previous study , explored the transcriptome of s. mansoni adult males obtaining 11 novel microexon genes ( megs ) , as well as mapping 989 and 1196 contigs to intergenic and intronic genomic regions , respectively . 
   this data could represent new protein - coding genes or noncoding rnas ( ncrnas ) . 
   together , these approaches have significantly advanced our understanding of the dynamics parasite transcriptomes [ 9 , 65 ] . 
   however , there is a need to polish and translate sequence data and gene expression profiles into functional information by computational predictions and experimental characterization . 
   the vast amount of available data opened a myriad of possibilities towards the elucidation of gene functions . 
   transcriptomics is also a key approach to study posttranscriptional regulatory mechanisms such as alternative and transsplicing [ 57 , 6668 ] . 
   alternative splicing of transcripts of secreted proteins , like megs and polymorphic mucin isoforms , has been largely studied in schistosomes [ 51 , 66 ] . 
   this posttranscriptional processing has been proposed as a distinct genetic system to generate protein variation that would allow parasite adaptation to the immune response of different hosts . 
   additionally , alternative splicing has been shown to generate protein variation involved in transcriptional control and splicing . in the case of smca150 , a spliceosome interacting transcriptional cofactor 
   , it could impact many other transcripts leading to several effects in the parasite , especially in sexual dimorphism . 
   spliced leader ( sl ) transsplicing has been shown to be an important posttranscriptional regulation mechanism for s. mansoni . 
   at least 11% of all transcripts has been described as undergoing transsplicing in this organism . 
   sl - rnas are small ncrnas , products of small intronless genes , transcribed by dna polymerase ii and tandemly repeated in the genome . differently from nematodes , 
   s. mansoni carries a single sl sequence , which is composed by 36 nucleotides with an 3-terminal aug codon . 
   although the role of transsplicing is poorly understood , there is an evidence suggesting that sl transsplicing would function providing an initiator methionine for translation initiation of some recipient mrnas in platyhelminthes . 
   this mechanism is also involved in the resolution of polycistronic operons in monocistronic transcripts in s. mansoni [ 19 , 70 ] . despite the great potential revealed by the increasing number of genome and transcriptome studies in schistosomes , there are still several schistosoma species that remain neglected . 
   in contrast to the vast amount of data available in public databases , limited data has been decoded in functional studies and/or in the development of successful tools to fight schistosomes . 
   some of them include the convolution of schistosomes life cycle , the complex interaction with their hosts , time and labor - demand functional studies , the difficulties to nurture the complete life cycle in vitro , and the absence of immortalized cell lines , which has delayed the development of transgenesis tools and models . 
   lately , the posttranscriptional suppression of genes through rna interference ( rnai ) techniques has been a promise to fetch progress on new interventions for schistosomiasis and other helminthiases . in 2003 
   simultaneously gene knockdown of glyceraldehyde-3-phosphate dehydrogenase ( gapdh ) and a glucose transporter ( sgtp1 ) in the larval stage ( sporocysts )   and cathepsin b in adult worms   of s. mansoni were reported . 
   currently , this powerful technique is widely used in schistosomes and has been employed in two studies of functional screening . 
   the first study encompassed the exposure of sporocysts by soaking parasites to dsrna targeting 33 genes , from calcium binding proteins , transcription factors , to receptors , and antioxidant enzymes . in this work , despite the efficacy of this tool to deliver suppression of 11 different genes , it showed that , in s. mansoni , there is a gene - to - gene variability and exposure to dsrna could trigger gene specific upregulation . 
   later , in a different study using electroporation to expose schistosomula to dsrna of 11 target genes ( expressed in distinct tissues ) , the efficiency of rnai in a target specific fashion was observed . 
   other issues with the use of rnai have been widely discussed , not only in schistosomes , but also in other helminth parasites , showing that care should be taken when conducting and evaluating such experiments . despite the difficulties in exploring gene function by rnai in schistosomes , 
   many proteases ( cathepsins and aminopeptidases ) [ 7779 ] , kinases , multidrug resistance transporters , and type v collagen , among other proteins have been studied in diverse life stages of s. japonicum and s. mansoni . 
   recently , this tool has been described targeting tetraspanin 2 in diverse developmental stages of s. haematobium indicating the rnai feasibility in this species . 
   tetraspanins belong to a family of integral membrane proteins present in the outer surface membranes of the parasite tegument . 
   studies have shown that tetraspanins play important roles in the tegument development , maturation , or stability . 
   importantly , the knockdown of peroxiredoxin   and thioredoxin glutathione reductase , antioxidant enzymes , were amongst the first reports of lethality after gene silencing in the parasite , demonstrating the potential of rnai on drug target discovery . 
   moreover , enzymes such as glutathione - s - transferases ( gst26 and gst28 ) , peroxiredoxins ( prx1 and prx2 ) , and superoxide dismutase have been shown to play important roles in the protection of s. mansoni sporocysts in the host - parasite interplay . 
   knockdown of those targets increased parasite susceptibility to oxidative stress and to intermediate host immune cells as described elsewhere . recently 
   researchers are developing new tools for the introduction and expression of homologous or heterologous gene constructs via lentiviruses , replication - defective retroviruses , transposons , retrotransposons , and dna plasmid vectors . 
   sophisticated systems applied to assess gene function in the parasite are being achieved [ 8891 ] . to date , 
   eggs and miracidia are indicated as the preferred life stages for successful transformation approaches in order to enter the germline . in summary 
   , results from such independent studies have shown that schistosome transgenesis works in all the developmental stages tested and that some success has been achieved in integrating genes into the germline [ 8892 ] . 
   altogether , the increasing information on schistosome genomes and transcriptomes is now raising the possibilities to better explore molecular techniques in the field of parasitology , genomics , and computational biology allowing the development of approaches to unravel mechanisms of parasite infection , host - parasite interaction , and so forth [ 21 , 23 , 24 ] . in order to accelerate both parasite research and development of effective tools for schistosomiasis diagnostics and treatment , 
   user - friendly databases have been created and made publicly available to the scientific community [ 9 , 9395 ] . here , we highlight some of these major resources . 
   schistodb integrates genome and proteome sequence data along with functional annotation of genes and gene products of s. haematobium , s. japonicum , and s. mansoni . 
   this resource also covers results from large - scale analysis including ests , metabolic pathways , and candidate drug targets . 
   helmcop ( helminth control and prevention ) integrates functional , structural , and comparative genomics data of helminths from different taxonomic groups and distinct hosts ( plant , animal , and human ) . 
   helmcop offers a comprehensive suite of structural and functional annotations to support comparative analyses and host - parasite interaction studies . 
   genedb is an annotation database that brings together data from a broad range of pathogens and closely related organisms . 
   genedb offers database - driven annotation tools and pipelines and includes manually curated information maintained by computational and biological scientists . 
   collectively , these computational resources support biological and biomedical research and open new frontiers in evolutionary and functional genomics , transcriptomics , and proteomics of schistosoma species and other parasites . besides biodiversity assessment at the molecular level 
   , these resources provide a framework for the identification and prioritization of vaccine and drug targets against human diseases . as the scientific community progresses in data integration and interpretation 
   , we will meet the goals of current and future initiatives to improve human health [ 9 , 12 , 23 , 24 ] . 
   the -omics studies came along with the aim to fill the gaps of long - established approaches , enabling the use of a broad range of experimental and computational methods and contributing to dissect the biological basis of host - parasite interaction , diagnostics improvement , and the discovery of new drug and vaccine targets . 
   nuclear and mitochondrial genomes of some schistosoma species were completely sequenced opening new frontiers for comparative analyses , which will improve our understanding of parasite biology and evolution . 
   other genomes to be analysed include schistosoma species from each of the six clades currently recognized , and other representatives of the schistosomatidae . 
   improving accuracy / quality of genome assembly and annotation will be crucial for such analyses . despite the efforts in the characterization of genomes and transcriptomes of distinct schistosoma species , many questions regarding the biology and evolution of this important taxon remain unanswered . 
   these difficulties might be due to the size of schistosome genomes ( ~10-times larger compared to protozoan parasites ) , the complexity of its life cycle , the presence of rare features in posttranscriptional regulation ( e.g. , transsplicing ) , and little integration of the current information available , among other reasons . 
   there is an urgent need for data integration to help interpreting the massive amount of data generated over the years in this and other areas or research . 
   we envision that , in the future , more transcriptomic and proteomic data will be used to improve the understanding of the origin and evolution of schistosomatidae . 
   the analysis of structural data generated by experimental or computational approaches will also shed light in the biodiversity of schistosomes at the molecular level . in conclusion , 
   the availability of schistosome genome and transcriptome data has provided an unprecedented resource for many research areas . 
   limitations do exist and should be addressed to allow advances in understanding schistosome biology and evolution and ultimately support vaccine and drug development against schistosomiasis .
summary: schistosomes are digenean blood flukes of aves and mammals comprising 23 species . 
   some species are causative agents of human schistosomiasis , the second major neglected disease affecting over 230 million people worldwide . 
   modern technologies including the sequencing and characterization of nucleic acids and proteins have allowed large - scale analyses of parasites and hosts , opening new frontiers in biological research with potential biomedical and biotechnological applications . 
   nuclear genomes of the three most socioeconomically important species ( s. haematobium , s. japonicum , and s. mansoni ) have been sequenced and are under intense investigation . 
   mitochondrial genomes of six schistosoma species have also been completely sequenced and analysed from an evolutionary perspective . 
   furthermore , dna barcoding of mitochondrial sequences is used for biodiversity assessment of schistosomes . despite the efforts in the characterization of schistosoma genomes and transcriptomes , many questions regarding the biology and evolution of this important taxon 
   remain unanswered . 
   this paper aims to discuss some advances in the schistosome research with emphasis on genomics and transcriptomics . 
   it also aims to discuss the main challenges of the current research and to point out some future directions in schistosome studies .