PHASTpep: Analysis Software for Discovery of Cell-Selective Peptides via Phage Display and Next-Generation Sequencing.
PHASTpep: Analysis Software for Discovery of Cell-Selective Peptides via Phage Display and Next-Generation Sequencing.
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DOI：
10.1371/journal.pone.0155244
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kelly KA
中科院分区：
文献类型：
--
作者：
Brinton LT;Bauknight DK;Dasa SS;Kelly KA
下一代测序增强了噬菌体展示过程，允许对生物扫描过程产生的数百万个序列进行量化。作为回应，许多有价值的分析程序被开发出来，专注于特异性和寻找目标基序或共识序列。对于靶向药物传递和分子成像，也有必要找到选择性的多肽-只针对感兴趣的细胞类型或组织。我们提出了一种新的分析策略和配套的软件，噬菌体分析选择性靶标多肽(PHASTpep)，它可以识别高度特异和选择性的多肽。利用这一过程，我们在体外和体内发现并验证了两个针对胰腺癌相关成纤维细胞的序列(HTTIPKV和APPIMSV)，这些细胞逃脱了使用先前存在的软件的识别。我们的选择性分析使我们有可能发现针对特定细胞类型的多肽，并避免其他细胞类型，通过规避全身使用的并发症来增强临床可译性。
Next-generation sequencing has enhanced the phage display process, allowing for the quantification of millions of sequences resulting from the biopanning process. In response, many valuable analysis programs focused on specificity and finding targeted motifs or consensus sequences were developed. For targeted drug delivery and molecular imaging, it is also necessary to find peptides that are selective—targeting only the cell type or tissue of interest. We present a new analysis strategy and accompanying software, PHage Analysis for Selective Targeted PEPtides (PHASTpep), which identifies highly specific and selective peptides. Using this process, we discovered and validated, both in vitro and in vivo in mice, two sequences (HTTIPKV and APPIMSV) targeted to pancreatic cancer-associated fibroblasts that escaped identification using previously existing software. Our selectivity analysis makes it possible to discover peptides that target a specific cell type and avoid other cell types, enhancing clinical translatability by circumventing complications with systemic use.