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Sci Adv ; 6(11): eaax2271, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32195335

RESUMO

Antibodies are essential for elucidating gene function. However, affordable technology for proteome-scale antibody generation does not exist. To address this, we developed Proteome Epitope Tag Antibody Library (PETAL) and its array. PETAL consists of 62,208 monoclonal antibodies (mAbs) against 15,199 peptides from diverse proteomes. PETAL harbors binders for a great multitude of proteins in nature due to antibody multispecificity, an intrinsic antibody feature. Distinctive combinations of 10,000 to 20,000 mAbs were found to target specific proteomes by array screening. Phenotype-specific mAb-protein pairs were found for maize and zebrafish samples. Immunofluorescence and flow cytometry mAbs for membrane proteins and chromatin immunoprecipitation-sequencing mAbs for transcription factors were identified from respective proteome-binding PETAL mAbs. Differential screening of cell surface proteomes of tumor and normal tissues identified internalizing tumor antigens for antibody-drug conjugates. By finding high-affinity mAbs at a fraction of current time and cost, PETAL enables proteome-scale antibody generation and target discovery.


Assuntos
Anticorpos Monoclonais Murinos/química , Epitopos/química , Proteoma/química , Células A549 , Animais , Células HEK293 , Células HL-60 , Células HeLa , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Células Jurkat , Células K562 , Células MCF-7 , Camundongos , Células PC-3 , Peptídeos , Células THP-1 , Células U937
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