Deep mutational scanning: assessing protein function on a massive scale

被引：146

作者：

Araya, Carlos L. ^{[1
]}

Fowler, Douglas M. ^{[1
]}

机构：

[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

来源：

TRENDS IN BIOTECHNOLOGY | 2011年 / 29卷 / 09期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ANALYSIS; NEXT-GENERATION; PHAGE DISPLAY; NUCLEOTIDE RESOLUTION; RAPID CONSTRUCTION; YEAST GENOME; LANDSCAPES; EVOLUTION; MUTAGENESIS; REPERTOIRE;

D O I：

10.1016/j.tibtech.2011.04.003

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Analysis of protein mutants is an effective means to understand their function. Protein display is an approach that allows large numbers of mutants of a protein to be selected based on their activity, but only a handful with maximal activity have been traditionally identified for subsequent functional analysis. However, the recent application of high-throughput sequencing (HTS) to protein display and selection has enabled simultaneous assessment of the function of hundreds of thousands of mutants that span the activity range from high to low. Such deep mutational scanning approaches are rapid and inexpensive with the potential for broad utility. In this review, we discuss the emergence of deep mutational scanning, the challenges associated with its use and some of its exciting applications.

引用

页码：435 / 442

页数：8

共 71 条

[11] Using T7 phage display to select GFP-based binders [J].

Dai, M. ;

Temirov, J. ;

Pesavento, E. ;

Kiss, C. ;

Velappan, N. ;

Pavlik, P. ;

Werner, J. H. ;

Bradbury, A. R. M. .

PROTEIN ENGINEERING DESIGN & SELECTION, 2008, 21 (07) :413-424

[12] Rapid interactome profiling by massive sequencing [J].

Di Niro, Roberto ;

Sulic, Ana-Marija ;

Mignone, Flavio ;

D'Angelo, Sara ;

Bordoni, Roberta ;

Iacono, Michele ;

Marzari, Roberto ;

Gaiotto, Tiziano ;

Lavric, Miha ;

Bradbury, Andrew R. M. ;

Biancone, Luigi ;

Zevin-Sonkin, Dina ;

De Bellis, Gianluca ;

Santoro, Claudio ;

Sblattero, Daniele .

NUCLEIC ACIDS RESEARCH, 2010, 38 (09) :e110-e110

[13] Next-Generation Phage Display: Integrating and Comparing Available Molecular Tools to Enable Cost-Effective High-Throughput Analysis [J].

Dias-Neto, Emmanuel ;

Nunes, Diana N. ;

Giordano, Ricardo J. ;

Sun, Jessica ;

Botz, Gregory H. ;

Yang, Kuan ;

Setubal, Joao C. ;

Pasqualini, Renata ;

Arap, Wadih .

PLOS ONE, 2009, 4 (12)

[14] Somatic mutations affect key pathways in lung adenocarcinoma [J].

Ding, Li ;

Getz, Gad ;

Wheeler, David A. ;

Mardis, Elaine R. ;

McLellan, Michael D. ;

Cibulskis, Kristian ;

Sougnez, Carrie ;

Greulich, Heidi ;

Muzny, Donna M. ;

Morgan, Margaret B. ;

Fulton, Lucinda ;

Fulton, Robert S. ;

Zhang, Qunyuan ;

Wendl, Michael C. ;

Lawrence, Michael S. ;

Larson, David E. ;

Chen, Ken ;

Dooling, David J. ;

Sabo, Aniko ;

Hawes, Alicia C. ;

Shen, Hua ;

Jhangiani, Shalini N. ;

Lewis, Lora R. ;

Hall, Otis ;

Zhu, Yiming ;

Mathew, Tittu ;

Ren, Yanru ;

Yao, Jiqiang ;

Scherer, Steven E. ;

Clerc, Kerstin ;

Metcalf, Ginger A. ;

Ng, Brian ;

Milosavljevic, Aleksandar ;

Gonzalez-Garay, Manuel L. ;

Osborne, John R. ;

Meyer, Rick ;

Shi, Xiaoqi ;

Tang, Yuzhu ;

Koboldt, Daniel C. ;

Lin, Ling ;

Abbott, Rachel ;

Miner, Tracie L. ;

Pohl, Craig ;

Fewell, Ginger ;

Haipek, Carrie ;

Schmidt, Heather ;

Dunford-Shore, Brian H. ;

Kraja, Aldi ;

Crosby, Seth D. ;

Sawyer, Christopher S. .

NATURE, 2008, 455 (7216) :1069-1075

[15] A three-dimensional model of the yeast genome [J].

Duan, Zhijun ;

Andronescu, Mirela ;

Schutz, Kevin ;

McIlwain, Sean ;

Kim, Yoo Jung ;

Lee, Choli ;

Shendure, Jay ;

Fields, Stanley ;

Blau, C. Anthony ;

Noble, William S. .

NATURE, 2010, 465 (7296) :363-367

[16] Real-Time DNA Sequencing from Single Polymerase Molecules [J].

Eid, John ;

Fehr, Adrian ;

Gray, Jeremy ;

Luong, Khai ;

Lyle, John ;

Otto, Geoff ;

Peluso, Paul ;

Rank, David ;

Baybayan, Primo ;

Bettman, Brad ;

Bibillo, Arkadiusz ;

Bjornson, Keith ;

Chaudhuri, Bidhan ;

Christians, Frederick ;

Cicero, Ronald ;

Clark, Sonya ;

Dalal, Ravindra ;

deWinter, Alex ;

Dixon, John ;

Foquet, Mathieu ;

Gaertner, Alfred ;

Hardenbol, Paul ;

Heiner, Cheryl ;

Hester, Kevin ;

Holden, David ;

Kearns, Gregory ;

Kong, Xiangxu ;

Kuse, Ronald ;

Lacroix, Yves ;

Lin, Steven ;

Lundquist, Paul ;

Ma, Congcong ;

Marks, Patrick ;

Maxham, Mark ;

Murphy, Devon ;

Park, Insil ;

Pham, Thang ;

Phillips, Michael ;

Roy, Joy ;

Sebra, Robert ;

Shen, Gene ;

Sorenson, Jon ;

Tomaney, Austin ;

Travers, Kevin ;

Trulson, Mark ;

Vieceli, John ;

Wegener, Jeffrey ;

Wu, Dawn ;

Yang, Alicia ;

Zaccarin, Denis .

SCIENCE, 2009, 323 (5910) :133-138

[17] Test of synergistic interactions among deleterious mutations in bacteria [J].

Elena, SF ;

Lenski, RE .

NATURE, 1997, 390 (6658) :395-398

[18] Coevolution of PDZ domain-ligand interactions analyzed by high-throughput phage display and deep sequencing [J].

Ernst, Andreas ;

Gfeller, David ;

Kan, Zhengyan ;

Seshagiri, Somasekar ;

Kim, Philip M. ;

Bader, Gary D. ;

Sidhu, Sachdev S. .

MOLECULAR BIOSYSTEMS, 2010, 6 (10) :1782-1790

[19] Flow-cytometric isolation of human antibodies from a nonimmune Saccharomyces cerevisiae surface display library [J].

Feldhaus, MJ ;

Siegel, RW ;

Opresko, LK ;

Coleman, JR ;

Feldhaus, JMW ;

Yeung, YA ;

Cochran, JR ;

Heinzelman, P ;

Colby, D ;

Swers, J ;

Graff, C ;

Wiley, HS ;

Wittrup, KD .

NATURE BIOTECHNOLOGY, 2003, 21 (02) :163-170

[20] Sequencing antibody repertoires The next generation [J].

Fischer, Nicolas .

MABS, 2011, 3 (01) :17-20

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