An array of 60,000 antibodies for proteome-scale antibody generation and target discovery
Zhaohui Wang, Yang Li, Bing Hou, Mira I. Pronobis, Mingqiao Wang, Yuemeng Wang, Guangcun Cheng, Weining Weng, Yiqiang Wang, Yanfang Tang, Xuefan Xu, Rong Pan, Lin Fei, Nan Wang, Ziqing Chen, Shiwei Wang, Z. Luyan, Yang‐Rui Li, Dongliang Huang, Li Jiang, Zhiqiang Wang, Wenfang Zeng, Ying Zhang, Xuemei Du, Ying Lin, Zhiqing Li, Qingyou Xia, Jing Geng, Huaping Dai, Yuan Yu, Xiaodong Zhao, Zheng Yuan, Jian Yan, Qinghua Nie, Xiquan Zhang, Kun Wang, Fulin Chen, Qin Zhang, Yuxian Zhu, Susan Zheng, Kenneth D. Poss, Sheng‐ce Tao, Xun Meng
Abstract
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.