RiboMiner: a toolset for mining multi-dimensional features of the translatome with ribosome profiling data

Background Ribosome profiling has been widely used for studies of translation under a large variety of cellular and physiological contexts. Many of these studies have greatly benefitted from a series of data-mining tools designed for dissection of the translatome from different aspects. However, as the studies of translation advance quickly, the current toolbox still falls in short, and more specialized tools are in urgent need for deeper and more efficient mining of the important and new features of the translation landscapes. Results Here, we present RiboMiner, a bioinformatics toolset for mining of multi-dimensional features of the translatome with ribosome profiling data. RiboMiner performs extensive quality assessment of the data and integrates a spectrum of tools for various metagene analyses of the ribosome footprints and for detailed analyses of multiple features related to translation regulation. Visualizations of all the results are available. Many of these analyses have not been provided by previous methods. RiboMiner is highly flexible, as the pipeline could be easily adapted and customized for different scopes and targets of the studies. Conclusions Applications of RiboMiner on two published datasets did not only reproduced the main results reported before, but also generated novel insights into the translation regulation processes. Therefore, being complementary to the current tools, RiboMiner could be a valuable resource for dissections of the translation landscapes and the translation regulations by mining the ribosome profiling data more comprehensively and with higher resolution. RiboMiner is freely available at https://github.com/xryanglab/RiboMiner and https://pypi.org/project/RiboMiner .

[1]  M. Zavolan,et al.  Protein synthesis rates and ribosome occupancies reveal determinants of translation elongation rates , 2018, bioRxiv.

[2]  Jianyang Zeng,et al.  Analysis of Ribosome Stalling and Translation Elongation Dynamics by Deep Learning. , 2017, Cell systems.

[3]  Jonathan S. Weissman,et al.  Plastid: nucleotide-resolution analysis of next-generation sequencing and genomics data , 2016, BMC Genomics.

[4]  R. Flavell,et al.  The Translation of Non-Canonical Open Reading Frames Controls Mucosal Immunity , 2018, Nature.

[5]  Yirong Wang,et al.  Recent advances in ribosome profiling for deciphering translational regulation. , 2020, Methods.

[6]  Weili Wang,et al.  Riborex: fast and flexible identification of differential translation from Ribo‐seq data , 2017, Bioinform..

[7]  Haitao Zhao,et al.  Survey of the translation shifts in hepatocellular carcinoma with ribosome profiling , 2019, Theranostics.

[8]  Rachel Green,et al.  High-precision analysis of translational pausing by ribosome profiling in bacteria lacking EFP. , 2015, Cell reports.

[9]  Bernd Bukau,et al.  Selective ribosome profiling as a tool for studying the interaction of chaperones and targeting factors with nascent polypeptide chains and ribosomes , 2013, Nature Protocols.

[10]  Fabio Lauria,et al.  riboWaltz: Optimization of ribosome P-site positioning in ribosome profiling data , 2017, bioRxiv.

[11]  Carl Kingsford,et al.  Using the Ribodeblur pipeline to recover A-sites from yeast ribosome profiling data. , 2018, Methods.

[12]  Xuerui Yang,et al.  Genome-wide assessment of differential translations with ribosome profiling data , 2016, Nature Communications.

[13]  U. Ohler,et al.  Ribo-seQC: comprehensive analysis of cytoplasmic and organellar ribosome profiling data , 2019, bioRxiv.

[14]  G. Portella,et al.  RNA G-quadruplexes at upstream open reading frames cause DHX36- and DHX9-dependent translation of human mRNAs , 2018, Genome Biology.

[15]  Gerben Menschaert,et al.  mQC: A post-mapping data exploration tool for ribosome profiling , 2019, Comput. Methods Programs Biomed..

[16]  Nicholas T. Ingolia Ribosome profiling: new views of translation, from single codons to genome scale , 2014, Nature Reviews Genetics.

[17]  Y. Pilpel,et al.  An Evolutionarily Conserved Mechanism for Controlling the Efficiency of Protein Translation , 2010, Cell.

[18]  Eivind Valen,et al.  Shoelaces: an interactive tool for ribosome profiling processing and visualization , 2018, BMC Genomics.

[19]  Jeffrey A. Hussmann,et al.  Ribosome Profiling: Global Views of Translation. , 2018, Cold Spring Harbor perspectives in biology.

[20]  Ulrike A. Friedrich,et al.  Selective ribosome profiling to study interactions of translating ribosomes in yeast , 2019, Nature Protocols.

[21]  Gunnar Rätsch,et al.  RiboDiff: detecting changes of mRNA translation efficiency from ribosome footprints , 2015, bioRxiv.

[22]  Audrey M. Michel,et al.  PausePred and Rfeet: webtools for inferring ribosome pauses and visualizing footprint density from ribosome profiling data , 2018, RNA.

[23]  Pascal Barbry,et al.  RiboProfiling: a Bioconductor package for standard Ribo-seq pipeline processing , 2016, F1000Research.

[24]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[25]  Henning Urlaub,et al.  EF-P Is Essential for Rapid Synthesis of Proteins Containing Consecutive Proline Residues , 2013, Science.

[26]  Tao Liu,et al.  Genome-wide identification and differential analysis of translational initiation , 2017, Nature Communications.

[27]  Tamir Tuller,et al.  stAIcalc: tRNA adaptation index calculator based on species-specific weights , 2016, Bioinform..

[28]  Xuerui Yang,et al.  Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis , 2017, Cell Research.

[29]  Z. Ignatova,et al.  eIF3 associates with 80S ribosomes to promote translation elongation, mitochondrial homeostasis, and muscle health , 2019, bioRxiv.

[30]  Binbin Shi,et al.  Ribosome elongating footprints denoised by wavelet transform comprehensively characterize dynamic cellular translation events , 2018, Nucleic acids research.

[31]  Audrey M. Michel,et al.  RiboGalaxy: A browser based platform for the alignment, analysis and visualization of ribosome profiling data , 2016, RNA biology.

[32]  D. Black Mechanisms of alternative pre-messenger RNA splicing. , 2003, Annual review of biochemistry.

[33]  Thomas Girke,et al.  systemPipeR: NGS workflow and report generation environment , 2016, BMC Bioinformatics.

[34]  Zhi Xie,et al.  Computational resources for ribosome profiling: from database to Web server and software , 2019, Briefings Bioinform..

[35]  Thomas J. Hardcastle,et al.  The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-seq data analysis , 2015, RNA.

[36]  Rachel Legendre,et al.  RiboTools: a Galaxy toolbox for qualitative ribosome profiling analysis , 2015, Bioinform..

[37]  Robert Nadon,et al.  Anota: Analysis of Differential Translation in Genome-wide Studies , 2011, Bioinform..

[38]  J. Goeman,et al.  Assessing the translational landscape of myogenic differentiation by ribosome profiling , 2015, Nucleic acids research.

[39]  Bernd Bukau,et al.  Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling , 2018, Nature.

[40]  Nikolaus Rajewsky,et al.  Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation , 2014, The EMBO journal.

[41]  Aviv Regev,et al.  A Regression-Based Analysis of Ribosome-Profiling Data Reveals a Conserved Complexity to Mammalian Translation. , 2015, Molecular cell.

[42]  Patrick B. F. O'Connor,et al.  Insights into the mechanisms of eukaryotic translation gained with ribosome profiling , 2016, Nucleic acids research.

[43]  W. Van Criekinge,et al.  PROTEOFORMER: deep proteome coverage through ribosome profiling and MS integration , 2014, Nucleic acids research.

[44]  Uwe Ohler,et al.  Detecting actively translated open reading frames in ribosome profiling data , 2015, Nature Methods.

[45]  Rachel Green,et al.  eIF 5 A stimulates eRF 1-mediated peptidyl-tRNA hydrolysis in translation termination , 2017 .

[46]  Nicholas T. Ingolia,et al.  Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling , 2009, Science.

[47]  Xuerui Yang,et al.  De novo annotation and characterization of the translatome with ribosome profiling data , 2017, bioRxiv.

[48]  Richard A. Olshen,et al.  Assessing gene-level translational control from ribosome profiling , 2013, Bioinform..