{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:23:03Z","timestamp":1776234183104,"version":"3.50.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1159943"],"award-info":[{"award-number":["1159943"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1605266"],"award-info":[{"award-number":["1605266"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1813963"],"award-info":[{"award-number":["1813963"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Graduate Research Fellowship"},{"name":"Albert M. Mattocks Chair"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Deep sequencing of antibody and related protein libraries after phage or yeast-surface display sorting is widely used to identify variants with increased affinity, specificity, and\/or improvements in key biophysical properties. Conventional approaches for identifying optimal variants typically use the frequencies of observation in enriched libraries or the corresponding enrichment ratios. However, these approaches disregard the vast majority of deep sequencing data and often fail to identify the best variants in the libraries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we present a method, Position-Specific Enrichment Ratio Matrix (PSERM) scoring, that uses entire deep sequencing datasets from pre- and post-selections to score each observed protein variant. The PSERM scores are the sum of the site-specific enrichment ratios observed at each mutated position. We find that PSERM scores are much more reproducible and correlate more strongly with experimentally measured properties than frequencies or enrichment ratios, including for multiple antibody properties (affinity and non-specific binding) for a clinical-stage antibody (emibetuzumab). We expect that this method will be broadly applicable to diverse protein engineering campaigns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>All deep sequencing datasets and code to perform the analyses presented within are available via https:\/\/github.com\/Tessier-Lab-UMich\/PSERM_paper.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad446","type":"journal-article","created":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T17:22:52Z","timestamp":1689873772000},"source":"Crossref","is-referenced-by-count":7,"title":["Position-Specific Enrichment Ratio Matrix scores predict antibody variant properties from deep sequencing data"],"prefix":"10.1093","volume":"39","author":[{"given":"Matthew D","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, University of Michigan , Ann Arbor, MI 48109-2200, United States"},{"name":"Biointerfaces Institute, University of Michigan , Ann Arbor, MI 48109-2200, United States"}]},{"given":"Marshall A","family":"Case","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Michigan , Ann Arbor, MI 48109-2200, United States"}]},{"given":"Emily K","family":"Makowski","sequence":"additional","affiliation":[{"name":"Biointerfaces Institute, University of Michigan , Ann Arbor, MI 48109-2200, United States"},{"name":"Department of Pharmaceutical Sciences, University of Michigan , Ann Arbor, MI 48109-2200, United States"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3220-007X","authenticated-orcid":false,"given":"Peter M","family":"Tessier","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Michigan , Ann Arbor, MI 48109-2200, United States"},{"name":"Biointerfaces Institute, University of Michigan , Ann Arbor, MI 48109-2200, United States"},{"name":"Department of Pharmaceutical Sciences, University of Michigan , Ann Arbor, MI 48109-2200, United States"},{"name":"Department of Biomedical Engineering, University of Michigan , Ann Arbor, MI 48109-2200, United States"},{"name":"Protein Folding Disease Initiative, University of Michigan , Ann Arbor, MI 48109-2200, United States"},{"name":"Michigan Alzheimer\u2019s Disease Center, University of Michigan , Ann Arbor, MI 48109-2200, United States"}]}],"member":"286","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"2023090508340845300_btad446-B1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s12859-016-1124-4","article-title":"Detection and sequence\/structure mapping of biophysical constraints to protein variation in saturated mutational libraries and protein sequence alignments with a dedicated server","volume":"17","author":"Abriata","year":"2016","journal-title":"BMC Bioinformatics"},{"key":"2023090508340845300_btad446-B2","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.23156","article-title":"Measuring the sequence-affinity landscape of antibodies with massively parallel titration curves","author":"Adams","year":"2016"},{"key":"2023090508340845300_btad446-B3","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1093\/nar\/gkz131","article-title":"Next-generation sequencing-guided identification and reconstruction of antibody CDR combinations from phage selection outputs","volume":"47","author":"Barreto","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2023090508340845300_btad446-B4","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12859-015-0590-4","article-title":"Software for the analysis and visualization of deep mutational scanning data","volume":"16","author":"Bloom","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"2023090508340845300_btad446-B5","doi-asserted-by":"crossref","first-page":"e0185056","DOI":"10.1371\/journal.pone.0185056","article-title":"BBMerge\u2014accurate paired shotgun read merging via overlap","volume":"12","author":"Bushnell","year":"2017","journal-title":"PLoS One"},{"key":"2023090508340845300_btad446-B6","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.1016\/j.cell.2022.05.029","article-title":"Designing antibodies as therapeutics","volume":"185","author":"Carter","year":"2022","journal-title":"Cell"},{"key":"2023090508340845300_btad446-B7","doi-asserted-by":"crossref","article-title":"Machine learning to predict continuous protein properties from simple binary sorting and deep sequencing data","author":"Case","DOI":"10.1101\/2023.06.09.544229"},{"key":"2023090508340845300_btad446-B8","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1093\/bioinformatics\/btp163","article-title":"Biopython: freely available python tools for computational molecular biology and bioinformatics","volume":"25","author":"Cock","year":"2009","journal-title":"Bioinformatics"},{"key":"2023090508340845300_btad446-B9","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1093\/protein\/gzu032","article-title":"From deep sequencing to actual clones","volume":"27","author":"D'Angelo","year":"2014","journal-title":"Protein Eng Des Sel"},{"key":"2023090508340845300_btad446-B10","doi-asserted-by":"crossref","first-page":"100508","DOI":"10.1016\/j.jbc.2021.100508","article-title":"Rational affinity maturation of anti-amyloid antibodies with high conformational and sequence specificity","volume":"296","author":"Desai","year":"2021","journal-title":"J Biol Chem"},{"key":"2023090508340845300_btad446-B11","doi-asserted-by":"crossref","first-page":"1701792","DOI":"10.1080\/19420862.2019.1701792","article-title":"Exploiting next-generation sequencing in antibody selections\u2014a simple PCR method to recover binders","volume":"12","author":"Ferrara","year":"2020","journal-title":"mAbs"},{"key":"2023090508340845300_btad446-B12","doi-asserted-by":"crossref","first-page":"523","DOI":"10.4161\/mabs.24979","article-title":"Deep mutational scanning of an antibody against epidermal growth factor receptor using mammalian cell display and massively parallel pyrosequencing","volume":"5","author":"Forsyth","year":"2013","journal-title":"mAbs"},{"key":"2023090508340845300_btad446-B13","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nmeth.1492","article-title":"High-resolution mapping of protein sequence-function relationships","volume":"7","author":"Fowler","year":"2010","journal-title":"Nat Methods"},{"key":"2023090508340845300_btad446-B14","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1093\/bioinformatics\/btr577","article-title":"Enrich: software for analysis of protein function by enrichment and depletion of variants","volume":"27","author":"Fowler","year":"2011","journal-title":"Bioinformatics"},{"key":"2023090508340845300_btad446-B15","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nmeth.3027","article-title":"Deep mutational scanning: a new style of protein science","volume":"11","author":"Fowler","year":"2014","journal-title":"Nat Methods"},{"key":"2023090508340845300_btad446-B16","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.sbi.2015.09.001","article-title":"Deep sequencing in library selection projects: what insight does it bring?","volume":"33","author":"Glanville","year":"2015","journal-title":"Curr Opin Struct Biol"},{"key":"2023090508340845300_btad446-B17","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.tips.2021.11.010","article-title":"Deep mutational scanning for therapeutic antibody engineering","volume":"43","author":"Hanning","year":"2022","journal-title":"Trends Pharmacol Sci"},{"key":"2023090508340845300_btad446-B18","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/0022-2836(94)90032-9","article-title":"Position-based sequence weights","volume":"243","author":"Henikoff","year":"1994","journal-title":"J Mol Biol"},{"key":"2023090508340845300_btad446-B19","doi-asserted-by":"crossref","first-page":"e0129125","DOI":"10.1371\/journal.pone.0129125","article-title":"Effective optimization of antibody affinity by phage display integrated with high-throughput DNA synthesis and sequencing technologies","volume":"10","author":"Hu","year":"2015","journal-title":"PLoS One"},{"key":"2023090508340845300_btad446-B20","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1073\/pnas.1616408114","article-title":"Biophysical properties of the clinical-stage antibody landscape","volume":"114","author":"Jain","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023090508340845300_btad446-B21","doi-asserted-by":"crossref","first-page":"E10342","DOI":"10.1073\/pnas.1812939115","article-title":"Peptide design by optimization on a data parameterized protein interaction landscape","volume":"115","author":"Jenson","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023090508340845300_btad446-B22","doi-asserted-by":"crossref","first-page":"45259","DOI":"10.1038\/srep45259","article-title":"Efficient affinity maturation of antibody variable domains requires co-selection of compensatory mutations to maintain thermodynamic stability","volume":"7","author":"Julian","year":"2017","journal-title":"Sci Rep"},{"key":"2023090508340845300_btad446-B23","doi-asserted-by":"crossref","first-page":"2153410","DOI":"10.1080\/19420862.2022.2153410","article-title":"Antibodies to watch in 2023","volume":"15","author":"Kaplon","year":"2023","journal-title":"mAbs"},{"key":"2023090508340845300_btad446-B24","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/s42003-021-02066-5","article-title":"CellectSeq: in silico discovery of antibodies targeting integral membrane proteins combining in situ selections and next-generation sequencing","volume":"4","author":"Kelil","year":"2021","journal-title":"Commun Biol"},{"key":"2023090508340845300_btad446-B25","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1073\/pnas.1614437114","article-title":"Trade-offs between enzyme fitness and solubility illuminated by deep mutational scanning","volume":"114","author":"Klesmith","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023090508340845300_btad446-B26","doi-asserted-by":"crossref","first-page":"21773","DOI":"10.1074\/jbc.M115.662783","article-title":"Deep sequencing-guided design of a high affinity dual specificity antibody to target two angiogenic factors in neovascular age-related macular degeneration","volume":"290","author":"Koenig","year":"2015","journal-title":"J Biol Chem"},{"key":"2023090508340845300_btad446-B27","doi-asserted-by":"crossref","first-page":"26457","DOI":"10.1074\/jbc.M115.676635","article-title":"Rapid fine conformational epitope mapping using comprehensive mutagenesis and deep sequencing","volume":"290","author":"Kowalsky","year":"2015","journal-title":"J Biol Chem"},{"key":"2023090508340845300_btad446-B28","doi-asserted-by":"crossref","first-page":"1725365","DOI":"10.1080\/19420862.2020.1725365","article-title":"A functional antibody cross-reactive to both human and murine cytotoxic T-lymphocyte-associated protein 4 via binding to an N-glycosylation epitope","volume":"12","author":"Li","year":"2020","journal-title":"mAbs"},{"key":"2023090508340845300_btad446-B29","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1002\/bit.26248","article-title":"Identification of highly selective MMP-14 inhibitory fabs by deep sequencing","volume":"114","author":"Lopez","year":"2017","journal-title":"Biotechnol Bioeng"},{"key":"2023090508340845300_btad446-B30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-019-0592-z","article-title":"Development of therapeutic antibodies for the treatment of diseases","volume":"27","author":"Lu","year":"2020","journal-title":"J Biomed Sci"},{"key":"2023090508340845300_btad446-B31","first-page":"233","article-title":"The global landscape of approved antibody therapies","volume":"5","author":"Lyu","year":"2022","journal-title":"Antib Ther"},{"key":"2023090508340845300_btad446-B32","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1038\/s41598-021-84637-4","article-title":"Potential neutralizing antibodies discovered for novel corona virus using machine learning","volume":"11","author":"Magar","year":"2021","journal-title":"Sci Rep"},{"key":"2023090508340845300_btad446-B33","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1093\/bioinformatics\/btr507","article-title":"FLASH: fast length adjustment of short reads to improve genome assemblies","volume":"27","author":"Mago\u010d","year":"2011","journal-title":"Bioinformatics"},{"key":"2023090508340845300_btad446-B34","doi-asserted-by":"crossref","first-page":"2146629","DOI":"10.1080\/19420862.2022.2146629","article-title":"Reduction of therapeutic antibody self-association using yeast-display selections and machine learning","volume":"14","author":"Makowski","year":"2022","journal-title":"mAbs"},{"key":"2023090508340845300_btad446-B35","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1038\/s41467-022-31457-3","article-title":"Co-optimization of therapeutic antibody affinity and specificity using machine learning models that generalize to novel mutational space","volume":"13","author":"Makowski","year":"2022","journal-title":"Nat Commun"},{"key":"2023090508340845300_btad446-B36","doi-asserted-by":"crossref","first-page":"1951426","DOI":"10.1080\/19420862.2021.1951426","article-title":"Highly sensitive detection of antibody nonspecific interactions using flow cytometry","volume":"13","author":"Makowski","year":"2021","journal-title":"mAbs"},{"key":"2023090508340845300_btad446-B37","doi-asserted-by":"crossref","first-page":"1177932220915240","DOI":"10.1177\/1177932220915240","article-title":"Discovering selected antibodies from deep-sequenced phage-display antibody library using ATTILA","volume":"14","author":"Maranh\u00e3o","year":"2020","journal-title":"Bioinform Biol Insights"},{"key":"2023090508340845300_btad446-B38","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/nature11500","article-title":"The spatial architecture of protein function and adaptation","volume":"491","author":"McLaughlin","year":"2012","journal-title":"Nature"},{"key":"2023090508340845300_btad446-B39","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1038\/s41467-018-06403-x","article-title":"Mapping protein selectivity landscapes using multi-target selective screening and next-generation sequencing of combinatorial libraries","volume":"9","author":"Naftaly","year":"2018","journal-title":"Nat Commun"},{"key":"2023090508340845300_btad446-B40","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.tips.2020.12.004","article-title":"Machine learning for biologics: opportunities for protein engineering, developability, and formulation","volume":"42","author":"Narayanan","year":"2021","journal-title":"Trends Pharmacol Sci"},{"key":"2023090508340845300_btad446-B41","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jim.2018.11.014","article-title":"Cross-species reactive monoclonal antibodies against the extracellular domains of the insulin receptor and IGF1 receptor","volume":"465","author":"\u00d8rstrup","year":"2019","journal-title":"J Immunol Methods"},{"key":"2023090508340845300_btad446-B42","doi-asserted-by":"crossref","first-page":"E7550","DOI":"10.1073\/pnas.1804015115","article-title":"Inferring the shape of global epistasis","volume":"115","author":"Otwinowski","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023090508340845300_btad446-B43","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bej.2018.06.003","article-title":"Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility","volume":"137","author":"Rabia","year":"2018","journal-title":"Biochem Eng J"},{"key":"2023090508340845300_btad446-B44","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1037\/1082-989X.1.2.178","article-title":"Comparing correlated but nonoverlapping correlations","volume":"1","author":"Raghunathan","year":"1996","journal-title":"Psychological Methods"},{"key":"2023090508340845300_btad446-B45","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.ymeth.2013.03.001","article-title":"Deep sequencing of phage display libraries to support antibody discovery","volume":"60","author":"Ravn","year":"2013","journal-title":"Methods"},{"key":"2023090508340845300_btad446-B46","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1093\/nar\/gkq789","article-title":"By-passing in vitro screening - next generation sequencing technologies applied to antibody display and in silico candidate selection","volume":"38","author":"Ravn","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023090508340845300_btad446-B47","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1016\/j.jmb.2014.09.025","article-title":"SORTCERY\u2014a high-throughput method to affinity rank peptide ligands","volume":"427","author":"Reich","year":"2015","journal-title":"J Mol Biol"},{"key":"2023090508340845300_btad446-B48","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fimmu.2018.00118","article-title":"Next-generation sequencing of antibody display repertoires","volume":"9","author":"Rouet","year":"2018","journal-title":"Front Immunol"},{"key":"2023090508340845300_btad446-B49","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13059-017-1272-5","article-title":"A statistical framework for analyzing deep mutational scanning data","volume":"18","author":"Rubin","year":"2017","journal-title":"Genome Biol"},{"key":"2023090508340845300_btad446-B50","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1038\/s41598-021-85274-7","article-title":"Antibody design using LSTM based deep generative model from phage display library for affinity maturation","volume":"11","author":"Saka","year":"2021","journal-title":"Sci Rep"},{"key":"2023090508340845300_btad446-B51","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1016\/j.celrep.2019.08.056","article-title":"Affinity maturation enhances antibody specificity but compromises conformational stability","volume":"28","author":"Shehata","year":"2019","journal-title":"Cell Rep"},{"key":"2023090508340845300_btad446-B52","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1038\/s41590-018-0235-7","article-title":"Recent progress in broadly neutralizing antibodies to HIV","volume":"19","author":"Sok","year":"2018","journal-title":"Nat Immunol"},{"key":"2023090508340845300_btad446-B53","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/s41586-022-04464-z","article-title":"ACE2 binding is an ancestral and evolvable trait of sarbecoviruses","volume":"603","author":"Starr","year":"2022","journal-title":"Nature"},{"key":"2023090508340845300_btad446-B54","doi-asserted-by":"crossref","first-page":"e16814","DOI":"10.1002\/aic.16814","article-title":"Directed evolution methods for overcoming trade-offs between protein activity and stability","volume":"66","author":"Stimple","year":"2020","journal-title":"AIChE J"},{"key":"2023090508340845300_btad446-B55","doi-asserted-by":"crossref","first-page":"lqab019","DOI":"10.1093\/nargab\/lqab019","article-title":"Sequencing error profiles of Illumina sequencing instruments","volume":"3","author":"Stoler","year":"2021","journal-title":"NAR Genom Bioinform"},{"key":"2023090508340845300_btad446-B56","doi-asserted-by":"crossref","first-page":"12091","DOI":"10.1073\/pnas.91.25.12091","article-title":"Detection of conserved segments in proteins: iterative scanning of sequence databases with alignment blocks","volume":"91","author":"Tatusov","year":"1994","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023090508340845300_btad446-B57","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev-bioeng-071114-040733","article-title":"Advances in antibody design","volume":"17","author":"Tiller","year":"2015","journal-title":"Annu Rev Biomed Eng"},{"key":"2023090508340845300_btad446-B58","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: fundamental algorithms for scientific computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat Methods"},{"key":"2023090508340845300_btad446-B59","doi-asserted-by":"crossref","first-page":"bbab516","DOI":"10.1093\/bib\/bbab516","article-title":"Heavy chain sequence-based classifier for the specificity of human antibodies","volume":"23","author":"Wang","year":"2022","journal-title":"Briefings in Bioinformatics"},{"key":"2023090508340845300_btad446-B60","doi-asserted-by":"crossref","first-page":"e1007207","DOI":"10.1371\/journal.pcbi.1007207","article-title":"Optimizing antibody affinity and stability by the automated design of the variable light-heavy chain interfaces","volume":"15","author":"Warszawski","year":"2019","journal-title":"PLoS Comput Biol"},{"key":"2023090508340845300_btad446-B61","doi-asserted-by":"crossref","first-page":"e0138956","DOI":"10.1371\/journal.pone.0138956","article-title":"High-throughput ligand discovery reveals a sitewise gradient of diversity in broadly evolved hydrophilic fibronectin domains","volume":"10","author":"Woldring","year":"2015","journal-title":"PLoS One"},{"key":"2023090508340845300_btad446-B62","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1021\/acssynbio.8b00486","article-title":"An automated data-driven pipeline for improving heterologous enzyme expression","volume":"8","author":"Wrenbeck","year":"2019","journal-title":"ACS Synth Biol"},{"key":"2023090508340845300_btad446-B63","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.sbi.2016.11.001","article-title":"Deep sequencing methods for protein engineering and design","volume":"45","author":"Wrenbeck","year":"2017","journal-title":"Curr Opin Struct Biol"},{"key":"2023090508340845300_btad446-B64","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s12866-015-0450-4","article-title":"Phasing amplicon sequencing on Illumina Miseq for robust environmental microbial community analysis","volume":"15","author":"Wu","year":"2015","journal-title":"BMC Microbiol"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btad446\/51202101\/btad446.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/9\/btad446\/51355803\/btad446.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/9\/btad446\/51355803\/btad446.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T04:35:17Z","timestamp":1693888517000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btad446\/7227716"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Wren","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":64,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btad446","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.10.548448","asserted-by":"object"}]},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9,1]]},"published":{"date-parts":[[2023,7,21]]},"article-number":"btad446"}}