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LSTrAP-Crowd: prediction of novel components of bacterial ribosomes with crowd-sourced analysis of RNA sequencing data

Benedict Hew,Q. Tan,W. Goh,Jonathan Wei Xiong Ng,K. Koh,Ryan Chieh Feng Rugdee,Z. Teng,Junjie Tan,Xi Yei,Qingxiong Tan,Ifa Syafiqah Binte Sulaiman,Seo Min Li Gilia,Erielle Marie Fajardo Villanueva,S. T. Nguyen,Dhira Anindya Putri,Jovi Tan Siying,Teo Yong Ren Johanan,Jia Tan,Koh Shao Ning,Gladys,Wei Wen Ong,Jia Rong Moo,Jace Koh,Peiqi Lim,Shook Wei Teoh,Pravin Tamilselvam,H. Hui,Y. X. Chua,Yook Kit Ow Yeong,Tay Jian Hua,M. Chong,Yusuke Sho,Bridget Jing Xing Tang,Carissa Yuwono Kwantalalu,Nur Afiqah Binte Mohammad Rizal,W. Tan,L. Chun,Sherianne Yen Tze Tan,Tan Ying,Audrey Michelle Luminary,Li-Jia Jia,Jolyn,Vanessa Lunardi,Ann Don Low,M. K. Abdul Rahim,Lin Ming,J. Ng,Han-Hsing Tsou,Cheryl Lim Jiayi,Teffarina Tay Hui Wen,Valerie Teo Fang Wei,Tan You Sheng Justin,Shellia Oktavina,Aaminatul Khalishah Binte Roslan,Natasha Cassandra Chee,Zoe Chen Hui Xin,Nhi Uyen Le Nguyen,Tristy Abigayle Marta,Poh Jia’En,A. Ying,Alena Tay Qi Ye,Chiu Wei Yeow Emile,Wong Xanaz,Xylon Wei Rui Lee,Wong Pei Wen Kelly,Zhenhua Tan,Vishalini Val R,Rayna Yip,C. Chua,K. Boon,Sriya Mulupuri,Liming Shan,Samantha Chee Suhui,Amanda Crystal Lee Wei Jin,Siew Choo Tey,Qi Ying Neo,Chan Yi Hue,Phua Tian Xin,Ana Ho Sze Qi,E. E. Rodrigues,Chan Mu En,Dynn Sim,M. Chee,A. Ho,A. hui,B. Wong,M. Zhao,Er Kian Ching Gabbie,Deng Zheyun Grace,X. Tan,Melissa Foong,Lim Qin Rui Rachel,A. Lim,Seow Jia Xuan,Rinta P. Reji,D. Menon,O. Xuan,Nicole,Ravi Keerthana,M. Wong,Zachary J D’Rozario,Shing Yee Lim,Nicholas Lee,Ying Ni,Ying-qi Lian,Jing Wen Poh,Ming Jern Adrian Lee,P. R. Chandran,Jia Xin Ngiaw,Herman Foo,Joash Poon,Tong Ling Chan,P. Ng,Ashlyn Xuanqi Ng,Z. Ong,Lee Wan Xuan Trena,Lim Shi Min Kristy,Yu Xuan Thng,Ong Si Yi Shirley,Sau Thi Chu,Shu Hua Samantha Lim,J. Ho,C. Phang,Victoria Toh Le Yi,P. Ng,Seetoh Wei Song,Manessa Nah Shue Ern,M. Mutwil

Published 2020 in BMC Biology

ABSTRACT

Bacterial resistance to antibiotics is a growing health problem that is projected to cause more deaths than cancer by 2050. Consequently, novel antibiotics are urgently needed. Since more than half of the available antibiotics target the structurally conserved bacterial ribosomes, factors involved in protein synthesis are thus prime targets for the development of novel antibiotics. However, experimental identification of these potential antibiotic target proteins can be labor-intensive and challenging, as these proteins are likely to be poorly characterized and specific to few bacteria. Here, we use a bioinformatics approach to identify novel components of protein synthesis. In order to identify these novel proteins, we established a Large-Scale Transcriptomic Analysis Pipeline in Crowd (LSTrAP-Crowd), where 285 individuals processed 26 terabytes of RNA-sequencing data of the 17 most notorious bacterial pathogens. In total, the crowd processed 26,269 RNA-seq experiments and used the data to construct gene co-expression networks, which were used to identify more than a hundred uncharacterized genes that were transcriptionally associated with protein synthesis. We provide the identity of these genes together with the processed gene expression data. We identified genes related to protein synthesis in common bacterial pathogens and thus provide a resource of potential antibiotic development targets for experimental validation. The data can be used to explore additional vulnerabilities of bacteria, while our approach demonstrates how the processing of gene expression data can be easily crowd-sourced.

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