{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:41:03Z","timestamp":1767706863043},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2006,3,7]],"date-time":"2006-03-07T00:00:00Z","timestamp":1141689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Genomics"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The medical community requires computational tools that distinguish missense genetic differences having phenotypic impact within the vast number of sense mutations that do not. Tools that do this will become increasingly important for those seeking to use human genome sequence data to predict disease, make prognoses, and customize therapy to individual patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>An approach, termed DETECTER, is proposed to identify sites in a protein sequence where amino acid replacements are likely to have a significant effect on phenotype, including causing genetic disease. This approach uses a model-dependent tool to estimate the normalized replacement rate at individual sites in a protein sequence, based on a history of those sites extracted from an evolutionary analysis of the corresponding protein family. This tool identifies sites that have higher-than-average, average, or lower-than-average rates of change in the lineage leading to the sequence in the population of interest. The rates are then combined with sequence data to determine the likelihoods that particular amino acids were present at individual sites in the evolutionary history of the gene family. These likelihoods are used to predict whether any specific amino acid replacements, if introduced at the site in a modern human population, would have a significant impact on fitness. The DETECTER tool is used to analyze the cystic fibrosis transmembrane conductance regulator (CFTR) gene family.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>In this system, DETECTER retrodicts amino acid replacements associated with the cystic fibrosis disease with greater accuracy than alternative approaches. While this result validates this approach for this particular family of proteins only, the approach may be applicable to the analysis of polymorphisms generally, including SNPs in a human population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2164-7-44","type":"journal-article","created":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T19:18:26Z","timestamp":1142018306000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Application of DETECTER, an evolutionary genomic tool to analyze genetic variation, to the cystic fibrosis gene family"],"prefix":"10.1186","volume":"7","author":[{"given":"Eric A","family":"Gaucher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danny W","family":"De Kee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A","family":"Benner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2006,3,7]]},"reference":[{"issue":"5569","key":"427_CR1","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1126\/science.1069863","volume":"296","author":"SA Benner","year":"2002","unstructured":"Benner SA, Caraco MD, Thomson JM, Gaucher EA: Planetary biology--paleontological, geological, and molecular histories of life. Science. 2002, 296 (5569): 864-868. 10.1126\/science.1069863.","journal-title":"Science"},{"issue":"4","key":"427_CR2","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1093\/genetics\/163.4.1549","volume":"163","author":"EA Gaucher","year":"2003","unstructured":"Gaucher EA, Miyamoto MM, Benner SA: Evolutionary, structural and biochemical evidence for a new interaction site of the leptin obesity protein. Genetics. 2003, 163 (4): 1549-1553.","journal-title":"Genetics"},{"issue":"1","key":"427_CR3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1741-7007-2-19","volume":"2","author":"EA Gaucher","year":"2004","unstructured":"Gaucher EA, Graddy LG, Li T, Simmen RC, Simmen FA, Schreiber DR, Liberles DA, Janis CM, Benner SA: The planetary biology of cytochrome P450 aromatases. BMC Biol. 2004, 2 (1): 19-10.1186\/1741-7007-2-19.","journal-title":"BMC Biol"},{"issue":"5248","key":"427_CR4","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1126\/science.271.5248.502","volume":"271","author":"UM Chandrasekharan","year":"1996","unstructured":"Chandrasekharan UM, Sanker S, Glynias MJ, Karnik SS, Husain A: Angiotensin II-forming activity in a reconstructed ancestral chymase. Science. 1996, 271 (5248): 502-505.","journal-title":"Science"},{"issue":"8","key":"427_CR5","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1021\/cr940469a","volume":"97","author":"SA Benner","year":"1997","unstructured":"Benner SA, Cannarozzi G, Gerloff D, Turcotte M, Chelvanayagam G: Bona Fide Predictions of Protein Secondary Structure Using Transparent Analyses of Multiple Sequence Alignments. Chem Rev. 1997, 97 (8): 2725-2844. 10.1021\/cr940469a.","journal-title":"Chem Rev"},{"issue":"8","key":"427_CR6","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/nrd1152","volume":"2","author":"DB Searls","year":"2003","unstructured":"Searls DB: Pharmacophylogenomics: genes, evolution and drug targets. Nat Rev Drug Discov. 2003, 2 (8): 613-623. 10.1038\/nrd1152.","journal-title":"Nat Rev Drug Discov"},{"issue":"21","key":"427_CR7","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1056\/NEJMoa040938","volume":"350","author":"TJ Lynch","year":"2004","unstructured":"Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA: Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004, 350 (21): 2129-2139. 10.1056\/NEJMoa040938.","journal-title":"N Engl J Med"},{"issue":"5676","key":"427_CR8","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1126\/science.1099314","volume":"304","author":"JG Paez","year":"2004","unstructured":"Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004, 304 (5676): 1497-1500. 10.1126\/science.1099314.","journal-title":"Science"},{"issue":"4922","key":"427_CR9","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1126\/science.2570460","volume":"245","author":"B Kerem","year":"1989","unstructured":"Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC: Identification of the cystic fibrosis gene: genetic analysis. Science. 1989, 245 (4922): 1073-1080.","journal-title":"Science"},{"issue":"4922","key":"427_CR10","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1126\/science.2475911","volume":"245","author":"JR Riordan","year":"1989","unstructured":"Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, Drumm ML, Iannuzzi MC, Collins FS, Lap-Chee T: Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989, 245 (4922): 1066-1073.","journal-title":"Science"},{"issue":"4922","key":"427_CR11","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1126\/science.2772657","volume":"245","author":"JM Rommens","year":"1989","unstructured":"Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan JR, Lap-Chee T, Collins FS: Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989, 245 (4922): 1059-1065.","journal-title":"Science"},{"issue":"7","key":"427_CR12","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/89631","volume":"8","author":"AG Therien","year":"2001","unstructured":"Therien AG, Grant FE, Deber CM: Interhelical hydrogen bonds in the CFTR membrane domain. Nat Struct Biol. 2001, 8 (7): 597-601. 10.1038\/89631.","journal-title":"Nat Struct Biol"},{"issue":"1","key":"427_CR13","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1006\/prep.2001.1612","volume":"25","author":"AG Therien","year":"2002","unstructured":"Therien AG, Glibowicka M, Deber CM: Expression and purification of two hydrophobic double-spanning membrane proteins derived from the cystic fibrosis transmembrane conductance regulator. Protein Expr Purif. 2002, 25 (1): 81-86. 10.1006\/prep.2001.1612.","journal-title":"Protein Expr Purif"},{"issue":"4","key":"427_CR14","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/prot.10611","volume":"54","author":"AW Partridge","year":"2004","unstructured":"Partridge AW, Therien AG, Deber CM: Missense mutations in transmembrane domains of proteins: phenotypic propensity of polar residues for human disease. Proteins. 2004, 54 (4): 648-656. 10.1002\/prot.10611.","journal-title":"Proteins"},{"issue":"11","key":"427_CR15","doi-asserted-by":"publisher","first-page":"3647","DOI":"10.1021\/bi0120502","volume":"41","author":"AW Partridge","year":"2002","unstructured":"Partridge AW, Melnyk RA, Deber CM: Polar residues in membrane domains of proteins: molecular basis for helix-helix association in a mutant CFTR transmembrane segment. Biochemistry. 2002, 41 (11): 3647-3653. 10.1021\/bi0120502.","journal-title":"Biochemistry"},{"issue":"5","key":"427_CR16","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/bip.10313","volume":"66","author":"AW Partridge","year":"2002","unstructured":"Partridge AW, Therien AG, Deber CM: Polar mutations in membrane proteins as a biophysical basis for disease. Biopolymers. 2002, 66 (5): 350-358. 10.1002\/bip.10313.","journal-title":"Biopolymers"},{"issue":"25","key":"427_CR17","doi-asserted-by":"publisher","first-page":"8077","DOI":"10.1021\/bi0494525","volume":"43","author":"MY Choi","year":"2004","unstructured":"Choi MY, Cardarelli L, Therien AG, Deber CM: Non-native interhelical hydrogen bonds in the cystic fibrosis transmembrane conductance regulator domain modulated by polar mutations. Biochemistry. 2004, 43 (25): 8077-8083. 10.1021\/bi0494525.","journal-title":"Biochemistry"},{"key":"427_CR18","unstructured":"Cystic Fibrosis Mutation Database. [http:\/\/www.genet.sickkids.on.ca\/cftr\/]"},{"issue":"4","key":"427_CR19","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/(SICI)1096-8628(19990212)82:4<329::AID-AJMG10>3.0.CO;2-D","volume":"82","author":"SE Hodge","year":"1999","unstructured":"Hodge SE, Lebo RV, Yesley AR, Cheney SM, Angle H, Milunsky J: Calculating posterior cystic fibrosis risk with echogenic bowel and one characterized cystic fibrosis mutation: avoiding pitfalls in the risk calculations. Am J Med Genet. 1999, 82 (4): 329-335. 10.1002\/(SICI)1096-8628(19990212)82:4<329::AID-AJMG10>3.0.CO;2-D.","journal-title":"Am J Med Genet"},{"issue":"3","key":"427_CR20","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0022-2836(02)00239-5","volume":"319","author":"K Fukami-Kobayashi","year":"2002","unstructured":"Fukami-Kobayashi K, Schreiber DR, Benner SA: Detecting compensatory covariation signals in protein evolution using reconstructed ancestral sequences. J Mol Biol. 2002, 319 (3): 729-743. 10.1016\/S0022-2836(02)00239-5.","journal-title":"J Mol Biol"},{"issue":"5","key":"427_CR21","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1101\/gr.176601","volume":"11","author":"PC Ng","year":"2001","unstructured":"Ng PC, Henikoff S: Predicting deleterious amino acid substitutions. Genome Res. 2001, 11 (5): 863-874. 10.1101\/gr.176601.","journal-title":"Genome Res"},{"issue":"3","key":"427_CR22","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1101\/gr.212802","volume":"12","author":"PC Ng","year":"2002","unstructured":"Ng PC, Henikoff S: Accounting for human polymorphisms predicted to affect protein function. Genome Res. 2002, 12 (3): 436-446. 10.1101\/gr.212802.","journal-title":"Genome Res"},{"issue":"13","key":"427_CR23","doi-asserted-by":"publisher","first-page":"3812","DOI":"10.1093\/nar\/gkg509","volume":"31","author":"PC Ng","year":"2003","unstructured":"Ng PC, Henikoff S: SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003, 31 (13): 3812-3814. 10.1093\/nar\/gkg509.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"427_CR24","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1093\/genetics\/141.4.1641","volume":"141","author":"Z Yang","year":"1995","unstructured":"Yang Z, Kumar S, Nei M: A new method of inference of ancestral nucleotide and amino acid sequences. Genetics. 1995, 141 (4): 1641-1650.","journal-title":"Genetics"},{"issue":"5","key":"427_CR25","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/nrg1324","volume":"5","author":"JW Thornton","year":"2004","unstructured":"Thornton JW: Resurrecting ancient genes: experimental analysis of extinct molecules. Nat Rev Genet. 2004, 5 (5): 366-375. 10.1038\/nrg1324.","journal-title":"Nat Rev Genet"},{"issue":"6955","key":"427_CR26","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature01977","volume":"425","author":"EA Gaucher","year":"2003","unstructured":"Gaucher EA, Thomson JM, Burgan MF, Benner SA: Inferring the palaeoenvironment of ancient bacteria on the basis of resurrected proteins. Nature. 2003, 425 (6955): 285-288. 10.1038\/nature01977.","journal-title":"Nature"},{"issue":"9","key":"427_CR27","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1093\/oxfordjournals.molbev.a004211","volume":"19","author":"BS Chang","year":"2002","unstructured":"Chang BS, Jonsson K, Kazmi MA, Donoghue MJ, Sakmar TP: Recreating a functional ancestral archosaur visual pigment. Mol Biol Evol. 2002, 19 (9): 1483-1489.","journal-title":"Mol Biol Evol"},{"issue":"2","key":"427_CR28","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0923-2508(00)00123-6","volume":"151","author":"SA Benner","year":"2000","unstructured":"Benner SA, Chamberlin SG, Liberles DA, Govindarajan S, Knecht L: Functional inferences from reconstructed evolutionary biology involving rectified databases--an evolutionarily grounded approach to functional genomics. Res Microbiol. 2000, 151 (2): 97-106. 10.1016\/S0923-2508(00)00123-6.","journal-title":"Res Microbiol"},{"key":"427_CR29","volume-title":"PAUP 4.0* - Phylogenetic Analysis Using Parsimony (*and Other Methods).","author":"DL Swofford","year":"1998","unstructured":"Swofford DL: PAUP 4.0* - Phylogenetic Analysis Using Parsimony (*and Other Methods). 1998, Sunderland, MA , Sinauer Associates"},{"issue":"5","key":"427_CR30","first-page":"555","volume":"13","author":"ZH Yang","year":"1997","unstructured":"Yang ZH: PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci Comput Appl Biosci. 1997, 13 (5): 555-556.","journal-title":"Comput Appl Biosci Comput Appl Biosci"},{"issue":"13","key":"427_CR31","doi-asserted-by":"publisher","first-page":"6676","DOI":"10.1073\/pnas.93.13.6676","volume":"93","author":"SC Li","year":"1996","unstructured":"Li SC, Goto NK, Williams KA, Deber CM: Alpha-helical, but not beta-sheet, propensity of proline is determined by peptide environment. Proc Natl Acad Sci U S A. 1996, 93 (13): 6676-6681. 10.1073\/pnas.93.13.6676.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"427_CR32","first-page":"208","volume-title":"Evolution of Genes and Proteins","author":"M Kimura","year":"1983","unstructured":"Kimura M: The neutral theory of molecular evolution. Evolution of Genes and Proteins. Edited by: Nei M, Koehn R. 1983, Sunderland, MA , Sinauer Associates, 208-233."},{"issue":"3","key":"427_CR33","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1002\/(SICI)1097-0134(199707)28:3<405::AID-PROT10>3.0.CO;2-L","volume":"28","author":"EL Sonnhammer","year":"1997","unstructured":"Sonnhammer EL, Eddy SR, Durbin R: Pfam: a comprehensive database of protein domain families based on seed alignments. Proteins. 1997, 28 (3): 405-420. 10.1002\/(SICI)1097-0134(199707)28:3<405::AID-PROT10>3.0.CO;2-L.","journal-title":"Proteins"},{"issue":"3","key":"427_CR34","first-page":"275","volume":"8","author":"DT Jones","year":"1992","unstructured":"Jones DT, Taylor WR, Thornton JM: The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci. 1992, 8 (3): 275-282.","journal-title":"Comput Appl Biosci"},{"issue":"6","key":"427_CR35","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0968-0004(02)02094-7","volume":"27","author":"EA Gaucher","year":"2002","unstructured":"Gaucher EA, Gu X, Miyamoto MM, Benner SA: Predicting functional divergence in protein evolution by site-specific rate shifts. Trends Biochem Sci. 2002, 27 (6): 315-321. 10.1016\/S0968-0004(02)02094-7.","journal-title":"Trends Biochem Sci"},{"issue":"11","key":"427_CR36","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/molbev\/msg171","volume":"20","author":"S Gribaldo","year":"2003","unstructured":"Gribaldo S, Casane D, Lopez P, Philippe H: Functional divergence prediction from evolutionary analysis: a case study of vertebrate hemoglobin. Mol Biol Evol. 2003, 20 (11): 1754-1759. 10.1093\/molbev\/msg171.","journal-title":"Mol Biol Evol"},{"issue":"2","key":"427_CR37","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1093\/oxfordjournals.molbev.a025594","volume":"13","author":"RL Goodwin","year":"1996","unstructured":"Goodwin RL, Baumann H, Berger FG: Patterns of divergence during evolution of alpha 1-proteinase inhibitors in mammals. Mol Biol Evol. 1996, 13 (2): 346-358.","journal-title":"Mol Biol Evol"},{"key":"427_CR38","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/0065-2571(91)90012-B","volume":"31","author":"SA Benner","year":"1991","unstructured":"Benner SA, Gerloff D: Patterns of divergence in homologous proteins as indicators of secondary and tertiary structure: a prediction of the structure of the catalytic domain of protein kinases. Adv Enzyme Regul. 1991, 31: 121-181.","journal-title":"Adv Enzyme Regul"},{"issue":"760","key":"427_CR39","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1126\/science.155.3760.279","volume":"155","author":"WM Fitch","year":"1967","unstructured":"Fitch WM, Margoliash E: Construction of phylogenetic trees. Science. 1967, 155 (760): 279-284.","journal-title":"Science"},{"issue":"6","key":"427_CR40","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1093\/hmg\/10.6.591","volume":"10","author":"S Sunyaev","year":"2001","unstructured":"Sunyaev S, Ramensky V, Koch I, Lathe W, Kondrashov AS, Bork P: Prediction of deleterious human alleles. Hum Mol Genet. 2001, 10 (6): 591-597. 10.1093\/hmg\/10.6.591.","journal-title":"Hum Mol Genet"},{"issue":"17","key":"427_CR41","doi-asserted-by":"publisher","first-page":"3894","DOI":"10.1093\/nar\/gkf493","volume":"30","author":"V Ramensky","year":"2002","unstructured":"Ramensky V, Bork P, Sunyaev S: Human non-synonymous SNPs: server and survey. Nucleic Acids Res. 2002, 30 (17): 3894-3900. 10.1093\/nar\/gkf493.","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"427_CR42","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1093\/bioinformatics\/16.9.760","volume":"16","author":"PC Ng","year":"2000","unstructured":"Ng PC, Henikoff JG, Henikoff S: PHAT: a transmembrane-specific substitution matrix. Predicted hydrophobic and transmembrane. Bioinformatics. 2000, 16 (9): 760-766. 10.1093\/bioinformatics\/16.9.760.","journal-title":"Bioinformatics"},{"issue":"4","key":"427_CR43","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1093\/oxfordjournals.molbev.a004113","volume":"19","author":"EA Gaucher","year":"2002","unstructured":"Gaucher EA, Das UK, Miyamoto MM, Benner SA: The crystal structure of eEF1A refines the functional predictions of an evolutionary analysis of rate changes among elongation factors. Mol Biol Evol. 2002, 19 (4): 569-573.","journal-title":"Mol Biol Evol"},{"issue":"1","key":"427_CR44","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/bioinformatics\/19.1.163","volume":"19","author":"F Glaser","year":"2003","unstructured":"Glaser F, Pupko T, Paz I, Bell RE, Bechor-Shental D, Martz E, Ben-Tal N: ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information. Bioinformatics. 2003, 19 (1): 163-164. 10.1093\/bioinformatics\/19.1.163.","journal-title":"Bioinformatics"},{"issue":"9","key":"427_CR45","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1093\/molbev\/msh194","volume":"21","author":"I Mayrose","year":"2004","unstructured":"Mayrose I, Graur D, Ben-Tal N, Pupko T: Comparison of site-specific rate-inference methods for protein sequences: empirical bayesian methods are superior. Mol Biol Evol. 2004, 21 (9): 1781-1791. 10.1093\/molbev\/msh194.","journal-title":"Mol Biol Evol"},{"issue":"2","key":"427_CR46","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1006\/jmbi.1996.0167","volume":"257","author":"O Lichtarge","year":"1996","unstructured":"Lichtarge O, Bourne HR, Cohen FE: An evolutionary trace method defines binding surfaces common to protein families. J Mol Biol. 1996, 257 (2): 342-358. 10.1006\/jmbi.1996.0167.","journal-title":"J Mol Biol"},{"issue":"6950","key":"427_CR47","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/nature01858","volume":"424","author":"JW Thomas","year":"2003","unstructured":"Thomas JW, Touchman JW, Blakesley RW, Bouffard GG, Beckstrom-Sternberg SM, Margulies EH, Blanchette M, Siepel AC, Thomas PJ, McDowell JC, Maskeri B, Hansen NF, Schwartz MS, Weber RJ, Kent WJ, Karolchik D, Bruen TC, Bevan R, Cutler DJ, Schwartz S, Elnitski L, Idol JR, Prasad AB, Lee-Lin SQ, Maduro VV, Summers TJ, Portnoy ME, Dietrich NL, Akhter N, Ayele K, Benjamin B, Cariaga K, Brinkley CP, Brooks SY, Granite S, Guan X, Gupta J, Haghighi P, Ho SL, Huang MC, Karlins E, Laric PL, Legaspi R, Lim MJ, Maduro QL, Masiello CA, Mastrian SD, McCloskey JC, Pearson R, Stantripop S, Tiongson EE, Tran JT, Tsurgeon C, Vogt JL, Walker MA, Wetherby KD, Wiggins LS, Young AC, Zhang LH, Osoegawa K, Zhu B, Zhao B, Shu CL, De Jong PJ, Lawrence CE, Smit AF, Chakravarti A, Haussler D, Green P, Miller W, Green ED: Comparative analyses of multi-species sequences from targeted genomic regions. Nature. 2003, 424 (6950): 788-793. 10.1038\/nature01858.","journal-title":"Nature"},{"issue":"17","key":"427_CR48","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","volume":"25","author":"SF Altschul","year":"1997","unstructured":"Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997, 25 (17): 3389-3402. 10.1093\/nar\/25.17.3389.","journal-title":"Nucleic Acids Res"},{"issue":"22","key":"427_CR49","doi-asserted-by":"publisher","first-page":"4673","DOI":"10.1093\/nar\/22.22.4673","volume":"22","author":"JD Thompson","year":"1994","unstructured":"Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994, 22 (22): 4673-4680.","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"427_CR50","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1093\/biomet\/76.2.297","volume":"76","author":"CM Hurvich","year":"1989","unstructured":"Hurvich CM, Tsai CL: Regression and Time-Series Model Selection in Small Samples. Biometrika. 1989, 76 (2): 297-307.","journal-title":"Biometrika"},{"issue":"5","key":"427_CR51","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1080\/10635150490522304","volume":"53","author":"D Posada","year":"2004","unstructured":"Posada D, Buckley TR: Model selection and model averaging in phylogenetics: Advantages of akaike information criterion and Bayesian approaches over likelihood ratio tests. Systematic Biology. 2004, 53 (5): 793-808. 10.1080\/10635150490522304.","journal-title":"Systematic Biology"},{"key":"427_CR52","unstructured":"DETECTER Script. [http:\/\/www.ffame.org\/software\/detecter.html]"}],"container-title":["BMC Genomics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2164-7-44.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2164-7-44\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2164-7-44.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T01:38:21Z","timestamp":1630460301000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcgenomics.biomedcentral.com\/articles\/10.1186\/1471-2164-7-44"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,7]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["427"],"URL":"https:\/\/doi.org\/10.1186\/1471-2164-7-44","relation":{},"ISSN":["1471-2164"],"issn-type":[{"value":"1471-2164","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3,7]]},"assertion":[{"value":"8 December 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2006","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2006","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"44"}}