General information | |||
TC004140 | Gene
The sequence from the iB fragment is matched against the genes from the official gene set. The matche(s) is/are visualizied in a genome browser. |
NC_007416.3: 1587008..1592203 | |
Sequence information | |||
Transcripts / Proteins (1) | Get mRNA sequence
Get CDS sequence Get protein sequence |
||
Ortholog information (from OrthoDB)
The information about the homolog genes in Drosophila
is provided by OrthoDB http://www.orthodb.org/.
The homologs are sorted according to their similarity score. For an orthology statement additional
analysis are required. | |||
Closest fly homologs |
|
TC004140 |
GO terms for Tribolium
-
{{ goTerm.term }} ({{ goTerm.evidence }}){{ goTerm.evidenceTooltip }}{{goTerm.showAll ? '[-]' : '[+]'}}Status: {{ goTerm.status }}
Evidence: {{ goTerm.evidence }} ({{ goTerm.evidenceTooltip }})
Reference: {{ goTerm.referenceText }}
Quotation: {{ goTerm.quotation }}
Submitter: {{ goTerm.name }}
There are no GO terms for Tribolium at the moment. You can help the community by providing some GO terms for this gene.
GO terms for the homologous Drosophila genes
Assign a GO term to this Tribolium gene by filling in the fields. Repeat to add several GO terms. Search AmiGO for the correct GO ID. Use only the most specific term - use "graph views" to browse related terms ("child terms" are more specific; the more general "parent" terms will be automatically linked). Only information based on Tribolium data should be entered - do not define terms just based on Drosophila knowledge. We will review this information and submit the annotation to the Gene Ontology consortium.
Gene | {{ goGene }} |
|
---|---|---|
GO ID | * {{ blurIdResult }} |
|
Evidence | {{ blurEvidenceResult }} |
|
Reference | * {{ blurReferenceResult }} |
|
Quotation | ||
Name | ||
Publish name | ||
{{ unavailableText }} |
* : mandatory fields
Attention! iBeetle is a first pass screen. Hence, the documented phenotypes need to be confirmed by independent experiments using non-overlapping dsRNA fragments! Phenotypes with a penetrance > 50% are frequently reproduced. See Schmitt-Engel et al. 2015 for details on reproducibility.
General information | ||||
iB_00666 | iB fragment
The sequence from the iB fragment is matched against the genes from the official gene set. The matche(s) is/are visualizied in a genome browser. |
Get FastA Get primers |
Pupal injection procedure
Day 0: 10 female pupae of the pBA19 strain (muscle enhancer trap line) were injected with dsRNA.
3 days post injection (dpi): Hatch control: Pupal and adult lethality as well as metamorphosis defects (molting, eclosion) were documented. For mating, 4 males of the black strain were added.
9 dpi: First egg-lay was collected and incubated for cuticle analysis. Adult lethality and egg production (reduced/ no egg-lay) was documented.
11 dpi: Second egg-lay was collected and incubated for embryonic muscle analysis. Adult lethality and egg production (reduced/ no egg-lay) were documented.
Note: The adult morphology was not analyzed systematically at 3/9/11 dpi. Only obvious phenotypes, visible without magnification, have been annotated.
13 dpi: Egg productivity and Ovary analysis
The percentage of hatched larvae was documented and not hatched larvae/ eggs were embedded for cuticle analysis (15 dpi).
In case of a reduction of egg production, 4 injected females were dissected to analyze the gross morphology of the ovaries.
14 dpi: Analysis of embryonic musculature and early embryonic development
Offspring of the injected females (hatched and not hatched larvae/ eggs) were analysed for embryonic lethality and muscle defects.
15 dpi: Analysis of larval instar 1 cuticle
Offspring of injected females were analysed and cuticle phenotypes were annotated.
22 dpi: Stink gland analysis
Documentation of defects in abdominal and thoracic stink glands (colour, size, content) of the injected femals.
Terms used in the pupal injection procedure
- larval pantagmatic defects
- At least two tagmata (head, thorax, abdomen or terminus) show similar/ comparable defects.
- empty eggs
- Just empty shells are visible, no cuticle has been developed.
- strong defects
- L1 cuticle larvae which show severe defects. These strong defects are subdivided into three categories
- strongly fragmented (cuticle crumbs)
- No segments or appendages are identifiable, only residues of cuticle and bristles can be identified.
- cuticle remnants (with unidentifiable segments)
- Segments or parts of appendages are recognizable, but identity is not clear.
- cuticle remnants (with some identifiable segments)
- At least one segment or appendage is clearly regonizable.
- number of eggs on slide
- affected embryos usually (not always) do not hatch. Only the not hatched were used for cuticle analysis.
For the embryonic muscle analysis the hatched as well as the not hatched were analysed. - total number of affected eggs/embryos/larvae
- Summary of all different phenotypes/ phenotypic series which were annotated.
- inside-out
- The L1 larva shows a partial or complete inversion., e.g. bristles, appendages or parts of the abdominal segments are inverted into the interior of the cuticle.
- starved
- Dissected females show a strong resorption of fatbody predominately in the abdomen and the oogenesis is blocked. These are considered as eventually lethal phenotypes and the blocked oogenesis probably a secondary defect due to starvation.
- eclosion not fulfilled
- The emergence of the adult from the pupa stage is interrupted. This phenotype shows pupal as well as adult features.
Lethality 11 days after pupal injection: 20.0% (includes death as pupa, adult)
eclosion not fulfilled (with pupal and adult features) - Number of animals showing the phenotype: 1 (3 dpi)adult lethality - Number of animals showing the phenotype: 1 (9 dpi)
egg chamber not present - Number of animals showing the phenotype: 4
Larval injection procedure
Day 0: 10 female L5-6 larvae of the D17Xhom strain (females express RFP in the eyes and in the CNS; pupae express GFP in the thorax) were injected with dsRNA.
11 days post injection (dpi): Pupal morphology Documentation of larval/ pupal death and defects of metamorphosis (eclosion, delayed development). Screening for alterations of pupal head and appendages, pupal thorax, pupal thoracic musculature, pupal legs, pupal wings, pupal abdomen and pupal genital lobes.
16 dpi: Adult morphology Documentation of larval/ pupal and adult death and defects of metamorphosis (eclosion, delayed development). Screening for alterations of adult head and appendages, adult thorax, adult elytra and hindwings, adult legs and cuticle properties. For mating 4 males of the black strain were added.
19 dpi: Sieving and egg-lay Documentation of adult lethality and enduring metamorphosis defects.
22 dpi: Ovary analysis (Fertility) In case of a reduction of egg production 4 females were dissected and the gross morphology of the ovaries were analysed.
41 dpi: Fertility and stink gland analysis Documentation of defects in abdominal and thoracic stink glands development (colour, size, content) of the injected females. Check for fertility of injected larvae (no or decreased offspring).
Terms used in the larval injection procedure
- pupal/ adult pantagmatic defects
- At least two tagmata (head, thorax, abdomen or terminus) show similar/ comparable defects.
- pupal molt not fulfilled
- The hatching from the larva to the pupa is interrupted. Either it dies as prepupa or the phenotype shows larval as well as pupal features.
- eclosion not fulfilled
- The emergence of the adult from the pupa stage is interrupted. This phenotype shows pupal as well as adult features.
- starved
- Dissected females show a strong resorption of fatbody predominately in the abdomen and the oogenesis is blocked. These are considered as eventually lethal phenotypes and the blocked oogenesis probably a secondary defect due to starvation.
Lethalities 11 days after larval injection: 0.0% (includes death as larva, prepupa, pupa)
Lethalities 22 days after larval injection: 100.0% (includes death as larva, prepupa, pupa, adult)
pupal molt delayed (still larva) - Number of animals showing the phenotype: 1 (16 dpi)
eclosion not fulfilled (died as pupa) - Number of animals showing the phenotype: 2 (16 dpi)
eclosion not fulfilled (with pupal and adult features) - Number of animals showing the phenotype: 3 (16 dpi)
eclosion not fulfilled (died as pupa) - Number of animals showing the phenotype: 1 (19 dpi)
wings partially blistered - Number of animals showing the phenotype: 8
- >TC004140 RA
MAGTDRVSL SDALSNVDV LDELPLPDE QPCIEAQPC SVVYQANFD TNFEDRNGF VTGIAKYIE EATVHASLN ELLEEGQEH AVMLYTWRC CSRAIPQPK SNEQPNRVE IYEKTVEVL APEVNKLLN FMYFQKKAI ERFFEEVKR LCHTEKRKD FVSEAYLLT LGKFINMFA VLDELKNMK SSVKNDYST YRRAAQFLK VMSDSQTLQ ESQNLSMFL ATQNKIRDA VKENLERIS GYEELLADV VNICVHMFE TKMYLTPSE KHMLVKVMG FGLFLMDSE LCNINKLDQ KKKLRLDRI DRIFKNLEV VPLFGDMQI APFNYIKRS KHFDPSKWP LSSSNTPSP QADLMVHLP QIRDDHVKY ISELARYSN EVTTTYKES GTDAENKET AELALRGLQ LLSEWTSVV TELYSWKLL HPTDHHQNK ECPQEAEEY ERATRYNYS DEEKFALIE VIAMIKGLQ VLMARMETV FTDAIRRNI YAELQDFVQ IILREPLRK AIKNKKDLI RSIIMSVRE TCADWQRGV EPTQDPALR GKKDDNGFN VKVPRRNVG PSSTQLYMV RTMLESLIA DKSGGKRTL RKDIDGQYL MQIDQFHKT SFYWNYLLS FSESLQQCC DLSQLWYRE FYLEMTMGR RINKCTVRH AHNEECNDL ITMEKRIQF PIDMSMPWI LTDHILKTK EPSMMEYVL YPLDLYNDS ALYALTIFR KQFLYDEVE AEVNLCFDQ FVYKLSEQI FAYYKQLAA SIFLDKRFR VECAALGAY LLPYPRANR YETLLKQRH VQLLGRSID LNKLITQRI NTDMQKSLD LAISKFEGG DITGVMELE GLLQVNRLC HKLLSKWLA LDDFDSMYR EANHNVLAP YGRITLHVF WELNYDFLP NYVYNAATN RFTKYRGQI AFAGAVHRD KPPQMSHHY MWGSKQLNL AYTTQYGQY SGFVGPQHF HTMCKLLGY QGIAVVMEE LLKIVKSLI QGNLLQFTK TLMEVMPKQ CKLPRYDYG SPGVLSYYH AQLNDIVQY PDARTELFH NFREFGNII LFCLLMEQA LSQEEVCDL LQAAPFQNI LPRPFCKEG EKPETKQKR LEAKYAALQ IVPNIEKLG TAKQSLISK EGDLLTRER LCCGLSIFE VVLNRLRTF LDDSVWVGP PPANGVMNV DECTEFHRL WSALQFVYC IPVSENEYT VEEMFGEGL HWAGCTMIV LLDQQRRFE ALDFCYHIL RVQRVDMKD EIVKGISLK RMVDRIRRF QVLNSQIFA ILNKFLKSS ENDELSVEH VRCFPPPVY PMNPQQHYH APEHLRQC
- >TC004140 RA
atggcagga actgatcga gtttcgctg agtgacgca ttatccaac gttgatgta ctagacgaa cttcctttg cctgatgaa caaccgtgc attgaggcc caaccttgc tcagttgtc tatcaggcg aattttgat acaaatttc gaagatcgg aacgggttt gtgacagga attgccaaa tacattgaa gaggcaaca gtacacgca agtctcaac gagttatta gaggaaggg caggagcat gctgtcatg ctctacacg tggaggtgc tgctctaga gccattcct cagcccaaa tctaacgaa caaccaaat cgggtcgaa atttacgag aaaactgtc gaagtgctc gcccccgaa gtgaacaaa ctcttgaac tttatgtat tttcaaaaa aaagcaatc gagcggttt ttcgaagaa gtaaaacga ttatgtcac accgaaaaa aggaaagac tttgtctca gaagcctat ctcctcact ttgggaaag ttcataaac atgtttgcc gtcttagac gagttaaaa aacatgaaa tcaagtgtc aaaaacgac tattccaca tacagaaga gcagcacaa tttttgaaa gtcatgtct gattcacaa acacttcaa gaatcacaa aatttatcg atgttctta gccacacaa aataaaatt agggatgct gttaaggag aatctggaa cgaatcagt ggctatgag gaattgcta gctgatgtt gtcaacatt tgcgtgcac atgtttgaa acgaaaatg tacctcaca cccagcgaa aaacacatg cttgttaaa gttatgggc ttcgggctt ttcctgatg gacagcgag ttgtgcaat attaataag ctagaccag aagaagaaa ttgaggctg gaccgcatt gaccggatt ttcaaaaac ttggaggtt gtccctttg ttcggggac atgcagatc gcccctttc aactacata aagcggagc aagcatttc gacccaagc aaatggcct ttatcaagt agcaatact ccctctccc caagccgat ttaatggta catttgccc caaattcgt gacgatcat gttaagtac ataagcgaa ttagcgcga tacagtaac gaagtcacg acaacatac aaagaaagc ggtactgac gctgaaaat aaagaaacg gccgaactt gcgctccgc ggattacaa ttactgtct gaatggaca agtgttgta acggaactg tattcatgg aagctttta cacccaact gaccaccat cagaataaa gagtgccca caagaggcc gaggaatac gaaagggcg acacggtat aattacagc gacgaggaa aaattcgcg ctaattgaa gtcattgcg atgattaag ggattacaa gtgctgatg gccagaatg gaaacggtg ttcactgac gcaattcgg cggaatatt tacgccgaa ttgcaagat ttcgtacag attattttg agggaaccg ctgaggaaa gcaattaaa aataaaaag gatcttatc agaagtatc attatgtcg gtgcgagaa acttgcgct gattggcag agaggtgtc gagccgact caagacccg gctttgagg ggcaaaaag gacgataac gggtttaat gttaaagtg ccaaggaga aacgtgggt ccttcctcc acccaactt tacatggtc aggacaatg ctggagtcg ctaattgcc gataaatca ggcggcaaa agaaccctg aggaaggac atagacggt caatattta atgcaaatt gaccagttc cacaaaacc tccttctac tggaattat cttctcagt ttcagtgaa tcgttgcag caatgttgc gacctgtcg cagctgtgg tacagagag ttctacctc gagatgacc atgggacgg agaataaac aaatgcacc gtgcgtcac gctcataac gaagaatgt aacgatttg atcacgatg gaaaaacgc atacaattc ccaatcgac atgtccatg ccttggatt ttgactgat catattttg aaaactaag gaaccctcg atgatggag tacgtcttg tacccgctt gatttatac aatgatagc gcgctttac gcactgaca atattccga aagcaattt ttatacgat gaggtcgag gctgaagtt aatttatgt tttgatcag tttgtttat aaactgagc gagcaaatt ttcgcgtac tataaacaa ctggcggca agtatcttt cttgataag cgcttcaga gtggagtgt gccgccttg ggggcttac ctgctcccc tacccgcga gcaaatcgt tacgaaacc ttgctaaaa cagcggcac gtccagtta ttagggcgg tcgatcgat ttgaataag ttgatcact cagaggatc aacaccgac atgcagaaa agtctcgat ttggcaata agtaagttc gaaggcggt gacataacc ggggttatg gaactggaa ggcctccta caagtgaat cggttgtgt cataaattg ctgagcaag tggctcgca cttgacgat ttcgattca atgtatcgt gaggctaat cacaacgtt ttggcgccc tatggccgc atcaccttg catgtgttt tgggagctg aactacgat ttcttgcct aattacgtc tacaatgcc gcgacgaac agatttact aagtatcgg gggcagatt gctttcgcg ggggctgtc cacagagat aagccgccg caaatgtcg catcattac atgtggggg agcaagcaa ctgaacctt gcctacacg actcagtat ggccaatat tccgggttc gtcgggcct cagcatttc cacacaatg tgcaaactc ttgggttat caaggcatt gcagttgtg atggaggag ctcctcaaa attgtcaaa agtctgatc caagggaac ctcctccaa ttcaccaaa actctaatg gaggtcatg ccaaagcag tgcaaattg ccacgttac gattacggc tcaccgggt gtgttaagt tactaccac gcccaattg aacgacatt gtccaatac cccgatgcc aggaccgag ttgttccac aatttccga gaatttggg aacattatc ctgttttgt ttactgatg gaacaggcc ttgtcacag gaggaagtc tgtgatttg ttgcaagcg gcaccgttt cagaatatc ctcccacgg ccgttttgc aaggaaggg gagaagccc gaaacgaag cagaaacgg cttgaagcc aaatatgcc gccttgcag attgtacca aatatagag aagttagga actgcaaag caatctttg atatcgaag gagggcgat ttattgacc cgtgagcgg ctgtgctgc ggtctctcg atttttgaa gttgttttg aaccgatta aggaccttc ctggacgat tcggtttgg gtcggaccg ccgcctgct aacggtgtc atgaacgtt gacgaatgc accgagttc catcgcttg tggtcggct ttacaattc gtctattgt attccagtt agcgagaac gaatatact gtcgaggaa atgtttggc gaaggtttg cattgggcg gggtgtaca atgatcgtg cttctggac cagcaaagg cggtttgag gccctcgat ttctgttac cacattctg agagtacaa agagttgac atgaaggat gaaattgtg aaaggcatt agcttgaag agaatggtg gacaggatc aggcgcttc caagtgctc aattcgcag atctttgcg attttgaac aagtttttg aagtcgagt gagaacgac gagttgtcg gttgaacat gtacgttgt ttcccgcca ccggtctac ccaatgaat ccgcaacag cactaccac gcacccgaa catctacgc cagtgttga
- >TC004140 RA
tagttttat atttgtcat ttgtttact tgtctaatg ccgcaccta aaaatgtta aatatttct aaaatagca caaaattag ttaagtttg ttgttgata acaaatagc cacgttctg ggccatgtt tctaagaat tgattaaat tattttctc tctggaaaa acagcaagt ggagtgctt gaaatggca ggaactgat cgagtttcg ctgagtgac gcattatcc aacgttgat gtactagac gaacttcct ttgcctgat gaacaaccg tgcattgag gcccaacct tgctcagtt gtctatcag gcgaatttt gatacaaat ttcgaagat cggaacggg tttgtgaca ggaattgcc aaatacatt gaagaggca acagtacac gcaagtctc aacgagtta ttagaggaa gggcaggag catgctgtc atgctctac acgtggagg tgctgctct agagccatt cctcagccc aaatctaac gaacaacca aatcgggtc gaaatttac gagaaaact gtcgaagtg ctcgccccc gaagtgaac aaactcttg aactttatg tattttcaa aaaaaagca atcgagcgg tttttcgaa gaagtaaaa cgattatgt cacaccgaa aaaaggaaa gactttgtc tcagaagcc tatctcctc actttggga aagttcata aacatgttt gccgtctta gacgagtta aaaaacatg aaatcaagt gtcaaaaac gactattcc acatacaga agagcagca caatttttg aaagtcatg tctgattca caaacactt caagaatca caaaattta tcgatgttc ttagccaca caaaataaa attagggat gctgttaag gagaatctg gaacgaatc agtggctat gaggaattg ctagctgat gttgtcaac atttgcgtg cacatgttt gaaacgaaa atgtacctc acacccagc gaaaaacac atgcttgtt aaagttatg ggcttcggg cttttcctg atggacagc gagttgtgc aatattaat aagctagac cagaagaag aaattgagg ctggaccgc attgaccgg attttcaaa aacttggag gttgtccct ttgttcggg gacatgcag atcgcccct ttcaactac ataaagcgg agcaagcat ttcgaccca agcaaatgg cctttatca agtagcaat actccctct ccccaagcc gatttaatg gtacatttg ccccaaatt cgtgacgat catgttaag tacataagc gaattagcg cgatacagt aacgaagtc acgacaaca tacaaagaa agcggtact gacgctgaa aataaagaa acggccgaa cttgcgctc cgcggatta caattactg tctgaatgg acaagtgtt gtaacggaa ctgtattca tggaagctt ttacaccca actgaccac catcagaat aaagagtgc ccacaagag gccgaggaa tacgaaagg gcgacacgg tataattac agcgacgag gaaaaattc gcgctaatt gaagtcatt gcgatgatt aagggatta caagtgctg atggccaga atggaaacg gtgttcact gacgcaatt cggcggaat atttacgcc gaattgcaa gatttcgta cagattatt ttgagggaa ccgctgagg aaagcaatt aaaaataaa aaggatctt atcagaagt atcattatg tcggtgcga gaaacttgc gctgattgg cagagaggt gtcgagccg actcaagac ccggctttg aggggcaaa aaggacgat aacgggttt aatgttaaa gtgccaagg agaaacgtg ggtccttcc tccacccaa ctttacatg gtcaggaca atgctggag tcgctaatt gccgataaa tcaggcggc aaaagaacc ctgaggaag gacatagac ggtcaatat ttaatgcaa attgaccag ttccacaaa acctccttc tactggaat tatcttctc agtttcagt gaatcgttg cagcaatgt tgcgacctg tcgcagctg tggtacaga gagttctac ctcgagatg accatggga cggagaata aacaaatgc accgtgcgt cacgctcat aacgaagaa tgtaacgat ttgatcacg atggaaaaa cgcatacaa ttcccaatc gacatgtcc atgccttgg attttgact gatcatatt ttgaaaact aaggaaccc tcgatgatg gagtacgtc ttgtacccg cttgattta tacaatgat agcgcgctt tacgcactg acaatattc cgaaagcaa tttttatac gatgaggtc gaggctgaa gttaattta tgttttgat cagtttgtt tataaactg agcgagcaa attttcgcg tactataaa caactggcg gcaagtatc tttcttgat aagcgcttc agagtggag tgtgccgcc ttgggggct tacctgctc ccctacccg cgagcaaat cgttacgaa accttgcta aaacagcgg cacgtccag ttattaggg cggtcgatc gatttgaat aagttgatc actcagagg atcaacacc gacatgcag aaaagtctc gatttggca ataagtaag ttcgaaggc ggtgacata accggggtt atggaactg gaaggcctc ctacaagtg aatcggttg tgtcataaa ttgctgagc aagtggctc gcacttgac gatttcgat tcaatgtat cgtgaggct aatcacaac gttttggcg ccctatggc cgcatcacc ttgcatgtg ttttgggag ctgaactac gatttcttg cctaattac gtctacaat gccgcgacg aacagattt actaagtat cgggggcag attgctttc gcgggggct gtccacaga gataagccg ccgcaaatg tcgcatcat tacatgtgg gggagcaag caactgaac cttgcctac acgactcag tatggccaa tattccggg ttcgtcggg cctcagcat ttccacaca atgtgcaaa ctcttgggt tatcaaggc attgcagtt gtgatggag gagctcctc aaaattgtc aaaagtctg atccaaggg aacctcctc caattcacc aaaactcta atggaggtc atgccaaag cagtgcaaa ttgccacgt tacgattac ggctcaccg ggtgtgtta agttactac cacgcccaa ttgaacgac attgtccaa taccccgat gccaggacc gagttgttc cacaatttc cgagaattt gggaacatt atcctgttt tgtttactg atggaacag gccttgtca caggaggaa gtctgtgat ttgttgcaa gcggcaccg tttcagaat atcctccca cggccgttt tgcaaggaa ggggagaag cccgaaacg aagcagaaa cggcttgaa gccaaatat gccgccttg cagattgta ccaaatata gagaagtta ggaactgca aagcaatct ttgatatcg aaggagggc gatttattg acccgtgag cggctgtgc tgcggtctc tcgattttt gaagttgtt ttgaaccga ttaaggacc ttcctggac gattcggtt tgggtcgga ccgccgcct gctaacggt gtcatgaac gttgacgaa tgcaccgag ttccatcgc ttgtggtcg gctttacaa ttcgtctat tgtattcca gttagcgag aacgaatat actgtcgag gaaatgttt ggcgaaggt ttgcattgg gcggggtgt acaatgatc gtgcttctg gaccagcaa aggcggttt gaggccctc gatttctgt taccacatt ctgagagta caaagagtt gacatgaag gatgaaatt gtgaaaggc attagcttg aagagaatg gtggacagg atcaggcgc ttccaagtg ctcaattcg cagatcttt gcgattttg aacaagttt ttgaagtcg agtgagaac gacgagttg tcggttgaa catgtacgt tgtttcccg ccaccggtc tacccaatg aatccgcaa cagcactac cacgcaccc gaacatcta cgccagtgt tgaagcacg tttatttta tacatttgt tggaatcag ctttcaaca ttttataat cttttatat ttattatag tcctactac atgtgtaaa tctcattac aaatgtatc gcccaccct catttatta tcggcctta ttggtattg ctttaattt ttcataata aaattttcg atgcctg
If you use iBeetle-Base, please cite: Dönitz J et al.: Expanded and updated data and a query pipeline for iBeetle-Base,
Nucleic Acids Res. 2018 Jan 4;46(D1):D831-D835. doi: 10.1093/nar/gkx984.
