ORFLine: a bioinformatic pipeline to prioritize small open reading frames identifies candidate secreted small proteins from lymphocytes

Hu, Fengyuan; Lu, Jinping; Matheson, Louise S.; Díaz-Muñoz, Manuel D.; Saveliev, Alexander; Xu, Jinbo; Turner, Martin

doi:10.1093/bioinformatics/btab339

Cited by 9 publications

(7 citation statements)

References 44 publications

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“…The recent development of approaches combining ribosome profiling (Ingolia et al, 2009), mass spectrometry, and computational analysis (J. Chen, Brunner, et al, 2020) has enable the identification of thousands open reading frames (ORFs) in lymphocytes encoding new proteins and small peptides with yet unknown functions (Turner et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

The RNA regulatory programs that govern lymphocyte development and function

Díaz-Muñoz

Osma-García

2021

WIREs RNA

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Lymphocytes require of constant and dynamic changes in their transcriptome for timely activation and production of effector molecules to combat external pathogens. Synthesis and translation of messenger (m)RNAs into these effector proteins is controlled both quantitatively and qualitatively by RNA binding proteins (RBPs). RBP-dependent regulation of RNA editing, subcellular location, stability, and translation shapes immune cell development and immunity.Extensive evidences have now been gathered from few model RBPs, HuR, PTBP1, ZFP36, and Roquin. However, recently developed methodologies for global characterization of protein:RNA interactions suggest the existence of complex RNA regulatory networks in which RBPs co-ordinately regulate the fate of sets of RNAs controlling cellular pathways and functions. In turn, RNA can also act as scaffolding of functionally related proteins modulating their activation and function. Here we review current knowledge about how RBPdependent regulation of RNA shapes our immune system and discuss about the existence of a hidden immune cell epitranscriptome.

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Section: Introductionmentioning

confidence: 99%

The RNA regulatory programs that govern lymphocyte development and function

Díaz-Muñoz

Osma-García

2021

WIREs RNA

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“…In recent years, various methods have been developed to explore smORFs [32,[46][47][48][49][50]. Construction of the smORF database in a specific organism typically begins with genome-wide scanning, resulting in a preliminary dataset.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel smORFs and microprotein acting in response to rehydration of Nostoc flagelliforme

2023

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Nostoc flagelliforme, a terrestrial cyanobacterium spread throughout arid and semi‐arid areas, has been long known for its outstanding adaptability to extremely dry conditions. This microorganism is able to recover biological activities within hours after months of anhydrobiosis state, attracting investigation through proteomic analysis. Except for canonical proteome, microproteins encoded by small ORFs (smORFs) have recently been regarded as indispensable participants in metabolic processes. However, the involvement of smORFs in N. flagelliforme remains unknown. Here we first constructed a smORF database in N. flagelliforme using bioinformatic prediction, resulting in 6072 novel smORFs. Then LS‐MS/MS analysis was applied to identify expression patterns of microproteins and seek smORFs and their encoded microprotein playing a role during rehydration. In total, 18 novel microproteins were mined based on a smORF searching strategy combined with three proteomic assays, of which five were annotated as ribosomal proteins, one as RNA polymerase subunit, and one as acetohydroxy acid isomeroreductase. We also suggested the possible functions of smORFs according to their expression pattern and discovered two neighboring and homologous smORFs. All these results will expand our knowledge of smORFs‐encoded microproteins and their relation to the stress response of extremophilic microorganisms.

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“…Transcriptomic data, which encompass the entire set of RNA transcripts in a given cell or tissue, provide valuable information about gene expression patterns and can aid in the identification of ORFs. Transcriptomic data can be obtained through methods such as RNA sequencing (RNA-seq) and, still nowadays, microarrays (Kiniry, Michel and Baranov, 2020;Hu et al, 2021). The integration of transcriptomic data with genomic sequences helps to refine ORF predictions by identifying expressed regions and providing evidence for the existence of functional genes.…”

Section: Input Data For Prediction Toolsmentioning

confidence: 99%

“…GeneScan utilizes Fourier techniques to detect the three-base periodicity in genomic sequences, aiding in recognizing coding regions (Tiwari et al, 1997). ORFLine, a computational pipeline, is adept at identifying and classifying sORFs, providing insights into potential secreted proteins from lymphocytes (Hu et al, 2021). It should be noted that all these methods may require extensive training datasets and might not be as universally applicable as ab initio, homology-based, or hybrid methods.…”

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confidence: 99%

Reference: OC/EFSA/GMO/2021/01: Refinement of the Risk Assessment Methodology for Open Reading Frames in GMO Applications

Daniele,

Penzo,

Evangelisti

et al. 2024

EFSA Supporting Publications

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A literature search was performed using PubMed to identify relevant studies on Open Reading Frames (ORFs) relevant to the risk assessment of GMOs. The collection of information on ORFs was steered by EFSA guidance for systematic reviews. The search queries allowed the retrieval a total of 15.484 non‐redundant references. The relevance of these documents was first assessed by screening titles and abstracts against specific inclusion and exclusion criteria related to risk assessment. This was followed by full‐text screening, which resulted in a total of 307 relevant documents. Information from these documents was extracted to emphasise criteria for the definition, prediction, and selection of ORFs, possibly highlighting the context of risk assessment of GMOs. Criteria such as codon identity, nucleotide composition, and mRNA secondary structure may be pertinent for developing new methods for risk assessment. However, the analysis revealed several limitations in the context of risk assessment, including the lack of structured data, diversity of application domains, paucity of information in food/feed, and the reliability of specific criteria for ORF definition, prediction and selection, among others. The analysis of prediction tools demonstrated that the generation of de novo experimental data or specific datasets is a critical factor. Nonetheless, certain features of ORF nucleotide sequences might prove useful in assessing the likelihood of expression of relevant ORFs for risk assessment of GMOs, but the criteria underlying this likelihood require further research and effort to be embedded in a tool. Bearing this in mind, and based on the information from the literature search, an evaluation was conducted regarding the potential of integrating various tools, their strengths and weaknesses and the challenge to integrate this knowledge into a single tool. A conceptual workflow is proposed for navigating these challenges and limitations and is presented as an attempt to integrate and streamline the tools and methods currently available.

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ORFLine: a bioinformatic pipeline to prioritize small open reading frames identifies candidate secreted small proteins from lymphocytes

Cited by 9 publications

References 44 publications

The RNA regulatory programs that govern lymphocyte development and function

The RNA regulatory programs that govern lymphocyte development and function

Identification of novel smORFs and microprotein acting in response to rehydration of Nostoc flagelliforme

Reference: OC/EFSA/GMO/2021/01: Refinement of the Risk Assessment Methodology for Open Reading Frames in GMO Applications

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