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Structural variations (SVs) play important roles in human evolution and diseases, but there is a lack of data resources concerning representative samples, especially for East Asians. Taking advantage of both next-generation sequencing and third-generation sequencing data at the whole-genome level, we developed the database PGG.SV to provide a practical platform for both regionally and globally representative structural variants. In its current version, PGG.SV archives 584 277 SVs obtained from whole-genome sequencing data of 6048 samples, including 1030 long-read sequencing genomes representing 177 global populations. PGG.SV provides (i) high-quality SVs with fine-scale and precise genomic locations in both GRCh37 and GRCh38, covering underrepresented SVs in existing sequencing and microarray data; (ii) hierarchical estimation of SV prevalence in geographical populations; (iii) informative annotations of SV-related genes, potential functions and clinical effects; (iv) an analysis platform to facilitate SV-based case-control association studies and (v) various visualization tools for understanding the SV structures in the human genome. Taken together, PGG.SV provides a user-friendly online interface, easy-to-use analysis tools and a detailed presentation of results. PGG.SV is freely accessible via https://www.biosino.org/pggsv.
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Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Genômica/métodos , Sequenciamento Completo do Genoma , Genoma Humano , Bases de Dados Genéticas , Variação Estrutural do Genoma , Análise de Sequência de DNA/métodosRESUMO
Understanding the relationship between fine-scale spatial organization and biological function necessitates a tool that effectively combines spatial positions, morphological information, and spatial transcriptomics (ST) data. We introduce the Spatial Multimodal Data Browser (SMDB, https://www.biosino.org/smdb), a robust visualization web service for interactively exploring ST data. By integrating multimodal data, such as hematoxylin and eosin (H&E) images, gene expression-based molecular clusters, and more, SMDB facilitates the analysis of tissue composition through the dissociation of two-dimensional (2D) sections and the identification of gene expression-profiled boundaries. In a digital three-dimensional (3D) space, SMDB allows researchers to reconstruct morphology visualizations based on manually filtered spots or expand anatomical structures using high-resolution molecular subtypes. To enhance user experience, it offers customizable workspaces for interactive exploration of ST spots in tissues, providing features like smooth zooming, panning, 360-degree rotation in 3D and adjustable spot scaling. SMDB is particularly valuable in neuroscience and spatial histology studies, as it incorporates Allen's mouse brain anatomy atlas for reference in morphological research. This powerful tool provides a comprehensive and efficient solution for examining the intricate relationships between spatial morphology, and biological function in various tissues.
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Perfilação da Expressão Gênica , Software , Animais , Camundongos , Encéfalo/anatomia & histologia , TranscriptomaRESUMO
Three prevalent SARS-CoV-2 variants of concern (VOCs) emerged and caused epidemic waves. It is essential to uncover advantageous mutations that cause the high transmissibility of VOCs. However, viral mutations are tightly linked, so traditional population genetic methods, including machine learning-based methods, cannot reliably detect mutations conferring a fitness advantage. In this study, we developed an approach based on the sequential occurrence order of mutations and the accelerated furcation rate in the pandemic-scale phylogenomic tree. We analyzed 3,777,753 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata using the Coronavirus GenBrowser. We found that two noncoding mutations at the same position (g.a28271-/u) may be crucial to the high transmissibility of Alpha, Delta, and Omicron VOCs although the noncoding mutations alone cannot increase viral transmissibility. Both mutations cause an A-to-U change at the core position -3 of the Kozak sequence of the N gene and significantly reduce the protein expression ratio of ORF9b to N. Using a convergent evolutionary analysis, we found that g.a28271-/u, S:p.P681H/R, and N:p.R203K/M occur independently on three VOC lineages, suggesting that coordinated changes of S, N, and ORF9b proteins are crucial to high viral transmissibility. Our results provide new insights into high viral transmissibility co-modulated by advantageous noncoding and nonsynonymous changes.
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COVID-19 , COVID-19/genética , SARS-CoV-2/genética , Evolução Biológica , Mutação , PandemiasRESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with a broad spectrum of histologic manifestations. The rapidly growing prevalence and the complex pathologic mechanisms of NAFLD pose great challenges for treatment development. Despite tremendous efforts devoted to drug development, there are no FDA-approved medicines yet. Here, we present NAFLDkb, a specialized knowledge base and platform for computer-aided drug design against NAFLD. With multiperspective information curated from diverse source materials and public databases, NAFLDkb presents the associations of drug-related entities as individual knowledge graphs. Practical drug discovery tools that facilitate the utilization and expansion of NAFLDkb have also been implemented in the web interface, including chemical structure search, drug-likeness screening, knowledge-based repositioning, and research article annotation. Moreover, case studies of a knowledge graph repositioning model and a generative neural network model are presented herein, where three repositioning drug candidates and 137 novel lead-like compounds were newly established as NAFLD pharmacotherapy options reusing data records and machine learning tools in NAFLDkb, suggesting its clinical reliability and great potential in identifying novel drug-disease associations of NAFLD and generating new insights to accelerate NAFLD drug development. NAFLDkb is freely accessible at https://www.biosino.org/nafldkb and will be updated periodically with the latest findings.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Reprodutibilidade dos Testes , Desenvolvimento de MedicamentosRESUMO
TransCirc (https://www.biosino.org/transcirc/) is a specialized database that provide comprehensive evidences supporting the translation potential of circular RNAs (circRNAs). This database was generated by integrating various direct and indirect evidences to predict coding potential of each human circRNA and the putative translation products. Seven types of evidences for circRNA translation were included: (i) ribosome/polysome binding evidences supporting the occupancy of ribosomes onto circRNAs; (ii) experimentally mapped translation initiation sites on circRNAs; (iii) internal ribosome entry site on circRNAs; (iv) published N-6-methyladenosine modification data in circRNA that promote translation initiation; (v) lengths of the circRNA specific open reading frames; (vi) sequence composition scores from a machine learning prediction of all potential open reading frames; (vii) mass spectrometry data that directly support the circRNA encoded peptides across back-splice junctions. TransCirc provides a user-friendly searching/browsing interface and independent lines of evidences to predicte how likely a circRNA can be translated. In addition, several flexible tools have been developed to aid retrieval and analysis of the data. TransCirc can serve as an important resource for investigating the translation capacity of circRNAs and the potential circRNA-encoded peptides, and can be expanded to include new evidences or additional species in the future.
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Adenosina/análogos & derivados , Bases de Dados de Ácidos Nucleicos , Biossíntese de Proteínas , RNA Circular/genética , Software , Adenosina/metabolismo , Genômica/métodos , Humanos , Sítios Internos de Entrada Ribossomal , Internet , Aprendizado de Máquina , Anotação de Sequência Molecular , Fases de Leitura Aberta , RNA Circular/química , RNA Circular/metabolismo , Ribossomos/genética , Ribossomos/metabolismoRESUMO
As the largest ethnic group in the world, the Han Chinese population is nonetheless underrepresented in global efforts to catalogue the genomic variability of natural populations. Here, we developed the PGG.Han, a population genome database to serve as the central repository for the genomic data of the Han Chinese Genome Initiative (Phase I). In its current version, the PGG.Han archives whole-genome sequences or high-density genome-wide single-nucleotide variants (SNVs) of 114 783 Han Chinese individuals (a.k.a. the Han100K), representing geographical sub-populations covering 33 of the 34 administrative divisions of China, as well as Singapore. The PGG.Han provides: (i) an interactive interface for visualization of the fine-scale genetic structure of the Han Chinese population; (ii) genome-wide allele frequencies of hierarchical sub-populations; (iii) ancestry inference for individual samples and controlling population stratification based on nested ancestry informative markers (AIMs) panels; (iv) population-structure-aware shared control data for genotype-phenotype association studies (e.g. GWASs) and (v) a Han-Chinese-specific reference panel for genotype imputation. Computational tools are implemented into the PGG.Han, and an online user-friendly interface is provided for data analysis and results visualization. The PGG.Han database is freely accessible via http://www.pgghan.org or https://www.hanchinesegenomes.org.
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Povo Asiático/genética , Bases de Dados Genéticas , Genética Populacional , Genoma Humano , Genômica , China , Etnicidade/genética , Genômica/métodos , Humanos , Software , Design de Software , NavegadorRESUMO
Yersinia enterocolitica is the most diverse species among the Yersinia genera and shows more polymorphism, especially for the non-pathogenic strains. Individual non-pathogenic Y. enterocolitica strains are wrongly identified because of atypical phenotypes. In this study, we isolated an unusual Y. enterocolitica strain LC20 from Rattus norvegicus. The strain did not utilize urea and could not be classified as the biotype. API 20E identified Escherichia coli; however, it grew well at 25 °C, but E. coli grew well at 37 °C. We analyzed the genome of LC20 and found the whole chromosome of LC20 was collinear with Y. enterocolitica 8081, and the urease gene did not exist on the genome which is consistent with the result of API 20E. Also, the 16 S and 23 SrRNA gene of LC20 lay on a branch of Y. enterocolitica. Furthermore, the core-based and pan-based phylogenetic trees showed that LC20 was classified into the Y. enterocolitica cluster. Two plasmids (80 and 50 k) from LC20 shared low genetic homology with pYV from the Yersinia genus, one was an ancestral Yersinia plasmid and the other was novel encoding a number of transposases. Some pathogenic and non-pathogenic Y. enterocolitica-specific genes coexisted in LC20. Thus, although it could not be classified into any Y. enterocolitica biotype due to its special biochemical metabolism, we concluded the LC20 was a Y. enterocolitica strain because its genome was similar to other Y. enterocolitica and it might be a strain with many mutations and combinations emerging in the processes of its evolution.
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Genoma Bacteriano/genética , Yersinia enterocolitica/classificação , Yersinia enterocolitica/genética , Animais , Sequência de Bases , Mapeamento Cromossômico , Hibridização Genômica Comparativa , Escherichia coli/genética , Filogenia , Plasmídeos , RNA Ribossômico 16S/genética , RNA Ribossômico 23S/genética , Ratos , Ureia/metabolismoRESUMO
Pan-genome analyses have shed light on the dynamics and evolution of bacterial genome from the point of population. The explosive growth of bacterial genome sequence also brought an extremely big challenge to pan-genome profile analysis. We developed a tool, named PanGP, to complete pan-genome profile analysis for large-scale strains efficiently. PanGP has integrated two sampling algorithms, totally random (TR) and distance guide (DG). The DG algorithm drew sample strain combinations on the basis of genome diversity of bacterial population. The performance of these two algorithms have been evaluated on four bacteria populations with strain numbers varying from 30 to 200, and the DG algorithm exhibited overwhelming advantage on accuracy and stability than the TR algorithm.
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Bactérias/genética , Genoma Bacteriano , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Algoritmos , Família Multigênica , SoftwareRESUMO
BACKGROUND: The data released by the 1000 Genomes Project contain an increasing number of genome sequences from different nations and populations with a large number of genetic variations. As a result, the focus of human genome studies is changing from single and static to complex and dynamic. The currently available human reference genome (GRCh37) is based on sequencing data from 13 anonymous Caucasian volunteers, which might limit the scope of genomics, transcriptomics, epigenetics, and genome wide association studies. DESCRIPTION: We used the massive amount of sequencing data published by the 1000 Genomes Project Consortium to construct the Virtual Chinese Genome Database (VCGDB), a dynamic genome database of the Chinese population based on the whole genome sequencing data of 194 individuals. VCGDB provides dynamic genomic information, which contains 35 million single nucleotide variations (SNVs), 0.5 million insertions/deletions (indels), and 29 million rare variations, together with genomic annotation information. VCGDB also provides a highly interactive user-friendly virtual Chinese genome browser (VCGBrowser) with functions like seamless zooming and real-time searching. In addition, we have established three population-specific consensus Chinese reference genomes that are compatible with mainstream alignment software. CONCLUSIONS: VCGDB offers a feasible strategy for processing big data to keep pace with the biological data explosion by providing a robust resource for genomics studies; in particular, studies aimed at finding regions of the genome associated with diseases.
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Bases de Dados de Ácidos Nucleicos , Genoma Humano , Povo Asiático/genética , China , Mapeamento Cromossômico , Biologia Computacional/métodos , Genética Populacional , Estudo de Associação Genômica Ampla , Genômica , Humanos , Polimorfismo de Nucleotídeo Único , Ferramenta de Busca , NavegadorRESUMO
The coronavirus disease 2019 (COVID-19) pandemic has dramatically increased the awareness of emerging infectious diseases. The advancement of multiomics analysis technology has resulted in the development of several databases containing virus information. Several scientists have integrated existing data on viruses to construct phylogenetic trees and predict virus mutation and transmission in different ways, providing prospective technical support for epidemic prevention and control. This review summarized the databases of known emerging infectious viruses and techniques focusing on virus variant forecasting and early warning. It focuses on the multi-dimensional information integration and database construction of emerging infectious viruses, virus mutation spectrum construction and variant forecast model, analysis of the affinity between mutation antigen and the receptor, propagation model of virus dynamic evolution, and monitoring and early warning for variants. As people have suffered from COVID-19 and repeated flu outbreaks, we focused on the research results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses. This review comprehensively viewed the latest virus research and provided a reference for future virus prevention and control research.
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OBJECTIVES: To investigate how BBIBP-CorV vaccination affecting antibody responses upon heterologous Omicron infection. METHODS: 440 Omicron-infected patients were recruited in this study. Antibodies targeting SARS-CoV-2 spike protein receptor binding domain (RBD) and nucleoprotein of both wild-type (WT) and Omicron were detected by ELISA. The clinical relevance was further analyzed. RESULTS: BBIBP-CorV vaccinated patients exhibited higher anti-RBD IgG levels targeting both WT and Omicron than non-vaccinated patients at different stages. By using a 3-day moving average analysis, we found that BBIBP-CorV vaccinated patients exhibited the increases in both anti-WT and Omicron RBD IgG from the onset and reached the plateau at Day 8 whereas those in non-vaccinated patients remained low during the disease. Significant increase in anti-WT RBD IgA was observed only in vaccinated patients. anti-Omicron RBD IgA levels remained low in both vaccinated and non-vaccinated patients. Clinically, severe COVID-19 only occurred in non-vaccinated group. anti-RBD IgG and IgA targeting both WT and Omicron were negatively correlated with virus load, hospitalization days and virus elimination in vaccinated patients. CONCLUSIONS: BBIBP-CorV vaccination effectively reduces the severity of Omicron infected patients. The existence of humoral memory responses established through BBIBP-CorV vaccination facilitates to induce rapid recall antibody responses when encountering SARS-CoV-2 variant infection.
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Antivirais , COVID-19 , Humanos , Anticorpos Antivirais , Formação de Anticorpos , China , COVID-19/prevenção & controle , Imunoglobulina A , Imunoglobulina G , SARS-CoV-2 , Vacinação , Estudos RetrospectivosRESUMO
SUMMARY: mRNA/miRNA-seq technology is becoming the leading technology to globally profile gene expression and elucidate the transcriptional regulation mechanisms in living cells. Although there are many tools available for analyzing RNA-seq data, few of them are available as easy accessible online web tools for processing both mRNA and miRNA data for the RNA-seq based user community. As such, we have developed a comprehensive web application tool for processing mRNA-seq and miRNA-seq data. Our web tool wapRNA includes four different modules: mRNA-seq and miRNA-seq sequenced from SOLiD or Solexa platform and all the modules were tested on previously published experimental data. We accept raw sequence data with an optional reads filter, followed by mapping and gene annotation or miRNA prediction. wapRNA also integrates downstream functional analyses such as Gene Ontology, KEGG pathway, miRNA targets prediction and comparison of gene's or miRNA's different expression in different samples. Moreover, we provide the executable packages for installation on user's local server. AVAILABILITY: wapRNA is freely available for use at http://waprna.big.ac.cn. The executable packages and the instruction for installation can be downloaded from our web site. CONTACT: husn@big.ac.cn; songshh@big.ac.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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MicroRNAs/química , RNA Mensageiro/química , Análise de Sequência de RNA/métodos , Software , Internet , MicroRNAs/metabolismo , RNA Mensageiro/metabolismoRESUMO
The outbreak of Coronavirus Disease 2019 (COVID-19) at the end of 2019 turned into a global pandemic. To help analyze the spread and evolution of the virus, we collated and analyzed data related to the viral genome, sequence variations, and locations in temporal and spatial distribution from GISAID. Information from the Wikipedia web page and published research papers were categorized and mined to extract epidemiological data, which was then integrated with the public dataset. Genomic and epidemiological data were matched with public information, and the data quality was verified by manual curation. Finally, an online database centered on virus genomic information and epidemiological data can be freely accessible at https://www.biosino.org/kgcov/ , which is helpful to identify relevant knowledge and devising epidemic prevention and control policies in collaboration with disease control personnel.
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COVID-19 , COVID-19/epidemiologia , COVID-19/genética , Surtos de Doenças , Genômica , Humanos , Pandemias , SARS-CoV-2RESUMO
MicroRNAs (miRNAs) are important regulators in gene expression. The dysregulation of miRNA expression is widely reported in the transformation from physiological to pathological states of cells. A large number of differentially expressed miRNAs (DEMs) have been identified in various human cancers by using high-throughput technologies, such as microarray and miRNA-seq. Through mining of published studies with high-throughput experiment information, the database of DEMs in human cancers (dbDEMC) was constructed with the aim of providing a systematic resource for the storage and query of the DEMs. Here we report an update of the dbDEMC to version 3.0, which contains two-fold more data entries than the second version and now includes also data from mice and rats. The dbDEMC 3.0 contains 3268 unique DEMs in 40 different cancer types. The current datasets for differential expression analysis have expanded to 9 generalized categories. Moreover, the current release integrates functional annotations of DEMs obtained by using experimentally validated targets. The annotations can be of great benefit to the intensive analysis of the roles of DEMs in cancer. In summary, dbDEMC 3.0 provides a valuable resource for characterizing molecular functions and regulatory mechanisms of DEMs in human cancers. The dbDEMC 3.0 is freely accessible at https://www.biosino.org/dbDEMC.
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Bases de Dados Genéticas , MicroRNAs , Neoplasias , Animais , Humanos , Camundongos , Ratos , Biologia Computacional , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genéticaRESUMO
Since the outbreak of SARS-CoV-2, antigenicity concerns continue to linger with emerging mutants. As recent variants have shown decreased reactivity to previously determined monoclonal antibodies (mAbs) or sera, monitoring the antigenicity change of circulating mutants is urgently needed for vaccine effectiveness. Currently, antigenic comparison is mainly carried out by immuno-binding assays. Yet, an online predicting system is highly desirable to complement the targeted experimental tests from the perspective of time and cost. Here, we provided a platform of SAS (Spike protein Antigenicity for SARS-CoV-2), enabling predicting the resistant effect of emerging variants and the dynamic coverage of SARS-CoV-2 antibodies among circulating strains. When being compared to experimental results, SAS prediction obtained the consistency of 100% on 8 mAb-binding tests with detailed epitope covering mutational sites, and 80.3% on 223 anti-serum tests. Moreover, on the latest South Africa escaping strain (B.1.351), SAS predicted a significant resistance to reference strain at multiple mutated epitopes, agreeing well with the vaccine evaluation results. SAS enables auto-updating from GISAID, and the current version collects 867K GISAID strains, 15.4K unique spike (S) variants, and 28 validated and predicted epitope regions that include 339 antigenic sites. Together with the targeted immune-binding experiments, SAS may be helpful to reduce the experimental searching space, indicate the emergence and expansion of antigenic variants, and suggest the dynamic coverage of representative mAbs/vaccines among the latest circulating strains. SAS can be accessed at https://www.biosino.org/sas.
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Glycosyltransferases (GTs), a large class of carbohydrate-active enzymes, adds glycosyl moieties to various substrates to generate multiple bioactive compounds, including natural products with pharmaceutical or agrochemical values. Here, we first collected comprehensive information on GTs, including amino acid sequences, coding region sequences, available tertiary structures, protein classification families, catalytic reactions and metabolic pathways. Then, we developed sequence search and molecular docking processes for GTs, resulting in a GTs database (GTDB). In the present study, 520 179 GTs from approximately 21 647 species that involved in 394 kinds of different reactions were deposited in GTDB. GTDB has the following useful features: (i) text search is provided for retrieving the complete details of a query by combining multiple identifiers and data sources; (ii) a convenient browser allows users to browse data by different classifications and download data in batches; (iii) BLAST is offered for searching against pre-defined sequences, which can facilitate the annotation of the biological functions of query GTs; and lastly, (iv) GTdock using AutoDock Vina performs docking simulations of several GTs with the same single acceptor and displays the results based on 3Dmol.js allowing easy view of models.
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Bases de Dados de Proteínas , Glicosiltransferases , Sequência de Aminoácidos , Ontologia Genética , Simulação de Acoplamento Molecular , Anotação de Sequência Molecular , Software , Interface Usuário-ComputadorRESUMO
Pharmacogenomics is the study of the impact of genetic variations or genotypes of individuals on their drug response or drug metabolism. Compared to traditional genomics research, pharmacogenomic research is more closely related to clinical practice. Pharmacogenomic discoveries may effectively assist clinicians and healthcare providers in determining the right drugs and proper dose for each patient, which can help avoid side effects or adverse reactions, and improve the drug therapy. Currently, pharmacogenomic approaches have proven their utility when it comes to the use of cardiovascular drugs, antineoplastic drugs, aromatase inhibitors, and agents used for infectious diseases. The rapid innovation in sequencing technology and genome-wide association studies has led to the development of numerous data resources and dramatically changed the landscape of pharmacogenomic research. Here we describe some of these web resources along with their names, web links, main contents, and our ratings.
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Bases de Dados Genéticas , Bases de Dados de Produtos Farmacêuticos , Internet , Farmacogenética , HumanosRESUMO
Polypeptides containing ≤100 amino acid residues (AAs) are generally considered to be small proteins (SPs). Many studies have shown that some SPs are involved in important biological processes, including cell signaling, metabolism, and growth. SP generally has a simple domain and has an advantage to be used as model system to overcome folding speed limits in protein folding simulation and drug design. But SPs were once thought to be trivial molecules in biological processes compared to large proteins. Because of the constraints of experimental methods and bioinformatics analysis, many genome projects have used a length threshold of 100 amino acid residues to minimize erroneous predictions and SPs are relatively under-represented in earlier studies. The general protein discovery methods have potential problems to predict and validate SPs, and very few effective tools and algorithms were developed specially for SPs identification. In this review, we mainly consider the diverse strategies applied to SPs prediction and discuss the challenge for differentiate SP coding genes from artifacts. We also summarize current large-scale discovery of SPs in species at the genome level. In addition, we present an overview of SPs with regard to biological significance, structural application, and evolution characterization in an effort to gain insight into the significance of SPs.