{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:43:44Z","timestamp":1753875824259,"version":"3.41.2"},"reference-count":9,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFF1204500"],"award-info":[{"award-number":["2023YFF1204500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62225307"],"award-info":[{"award-number":["62225307"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Massively Parallel Reporter Assays (MPRAs) have emerged as pivotal tools for systematically profiling cis-regulatory element activity, playing critical roles in deciphering gene regulation mechanisms and synthetic regulatory element engineering. However, MPRA experiments involve multi-step library processing procedures coupled with high-throughput sequencing. Operational errors during these complex workflows can lead to substantial resource depletion and experimental delays. Thus robust and user-friendly quality control methods are essential to minimize experimental failures and ensure reproducibility between replicates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here, we present esMPRA, an integrated quality control and analysis pipeline designed for MPRA experiments. Building on our experience in MPRA and its derivative techniques, coupled with systematic analysis of public MPRA datasets, we established standardized quality control metrics and developed a stepwise quality monitoring framework. esMPRA generates stage-specific diagnostic reports and provides experimental recommendations to avoid potential risks throughout the workflow. Designed for maximal accessibility, esMPRA features a one-line command-line interface and requires minimal bioinformatics expertise. Beyond quality assessment, the pipeline delivers processed data outputs, comprehensive analysis reports, and interface files compatible with downstream analyses, establishing an end-to-end solution for MPRA experimentation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>esMPRA is released as an open-source software under the MIT license. The source code for esMPRA is available on Zenodo (DOI: 10.5281\/zenodo.15362711) and GitHub (https:\/\/github.com\/WangLabTHU\/esMPRA\/) for Linux, macOS, and Windows and is available via PyPI as esMPRA. Data for testing and reference is available via Zenodo repository at https:\/\/zenodo.org\/records\/15034449.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf315","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T15:04:18Z","timestamp":1747839858000},"source":"Crossref","is-referenced-by-count":0,"title":["esMPRA: an easy-to-use systematic pipeline for MPRA experiment quality control and data analysis"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9038-9010","authenticated-orcid":false,"given":"Jiaqi","family":"Li","sequence":"first","affiliation":[{"name":"Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bioinformatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-3478","authenticated-orcid":false,"given":"Pengcheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bioinformatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Xi","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bioinformatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-8036","authenticated-orcid":false,"given":"Xiaowo","family":"Wang","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bioinformatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University , Beijing 100084,","place":["China"]},{"name":"College of Artificial Intelligence, Tsinghua University , Beijing 100084,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"2025070408320835000_btaf315-B1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s13059-019-1787-z","article-title":"MPRAnalyze: statistical framework for massively parallel reporter assays","volume":"20","author":"Ashuach","year":"2019","journal-title":"Genome Biol"},{"key":"2025070408320835000_btaf315-B2","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/s41586-024-07662-z","article-title":"Position-dependent function of human sequence-specific transcription factors","volume":"631","author":"Duttke","year":"2024","journal-title":"Nature"},{"key":"2025070408320835000_btaf315-B3","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/s41586-024-08070-z","article-title":"Machine-guided design of cell-type-targeting cis-regulatory elements","volume":"634","author":"Gosai","year":"2024","journal-title":"Nature"},{"key":"2025070408320835000_btaf315-B4","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/s41587-020-0584-2","article-title":"Automated design of thousands of nonrepetitive parts for engineering stable genetic systems","volume":"38","author":"Hossain","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2025070408320835000_btaf315-B5","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1038\/s41467-019-12794-2","article-title":"Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy","volume":"10","author":"Huang","year":"2019","journal-title":"Nat Commun"},{"key":"2025070408320835000_btaf315-B6","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1038\/s41467-025-56749-2","article-title":"Modeling and designing enhancers by introducing and harnessing transcription factor binding units","volume":"16","author":"Li","year":"2025","journal-title":"Nat Commun"},{"key":"2025070408320835000_btaf315-B7","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":"2025070408320835000_btaf315-B8","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/nbt.2205","article-title":"Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters","volume":"30","author":"Sharon","year":"2012","journal-title":"Nat Biotechnol"},{"key":"2025070408320835000_btaf315-B9","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1016\/j.cell.2016.04.027","article-title":"Direct identification of hundreds of Expression-Modulating variants using a multiplexed reporter assay","volume":"165","author":"Tewhey","year":"2016","journal-title":"Cell"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btaf315\/63264629\/btaf315.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/6\/btaf315\/63264629\/btaf315.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/41\/6\/btaf315\/63264629\/btaf315.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T12:32:20Z","timestamp":1751632340000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btaf315\/8139935"}},"subtitle":[],"editor":[{"given":"Can","family":"Alkan","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":9,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6,2]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btaf315","relation":{},"ISSN":["1367-4811"],"issn-type":[{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,5,21]]},"article-number":"btaf315"}}