Zhejiang U | College of Pharmaceutical Sciences | 中文版
IDRB: Softwares

Our experiences on software development have led to several pharmacoinformatics servers as follows:

  NOREVA: NORmalization and EVAluation of MS-based metabolomics data
    Server URL: https://idrblab.org/noreva/

    Diverse forms of unwanted signal variations in mass spectrometry-based metabolomics data adversely affect the accuracies of metabolic profiling. A variety of normalization methods have been developed for addressing this problem. However, their performances vary greatly and depend heavily on the nature of the studied data. Moreover, given the complexity of the actual data, it is not feasible to assess the performance of methods by single criterion. We therefore developed NOREVA to enable performance evaluation of various normalization methods from multiple perspectives. NOREVA integrated five well-established criteria (each with a distinct underlying theory) to ensure more comprehensive evaluation than any single criterion. It provided the most complete set of the available normalization methods, with unique features of removing overall unwanted variations based on quality control metabolites and allowing quality control samples based correction sequentially followed by data normalization. The originality of NOREVA and the reliability of its algorithms were extensively validated by case studies on five benchmark datasets. In sum, NOREVA is distinguished for its capability of identifying the well performed normalization method by taking multiple criteria into consideration and can be an indispensable complement to other available tools. NOREVA can be freely accessed at http://server.idrb.cqu.edu.cn/noreva/.

    Our Publication(s) Describing This Server:

  1. J. B. Fu, Y. Zhang, Y. X. Wang, H. N. Zhang, J. Liu, J. Tang, Q. X. Yang, H. C. Sun, W. Q. Qiu, Y. H. Ma, Z. R. Li, M. Y. Zheng, F. Zhu*. Optimization of metabolomic data processing using NOREVA. Nature Protocols (impact factor of the publication year: 13.491, 生物一区 TOP 期刊). doi: 10.1038/s41596-021-00636-9 (2021).
  2. Q. X. Yang, Y. X. Wang, Y. Zhang, F. C. Li, W. Q. Xia, Y. Zhou, Y. Q. Qiu, H. L. Li, F. Zhu*. NOREVA: enhanced normalization and evaluation of time-course and multi-class metabolomic data. Nucleic Acids Research (impact factor of the publication year: 11.501, 生物一区 TOP 期刊). 48(W1): 436-448 (2020).  
  3. Media Coverage & News Report:

  4. B. Li, J. Tang, Q. X. Yang, S. Li, X. J. Cui, Y. H. Li, Y. Z. Chen, W. W. Xue, X. F. Li, F. Zhu*. NOREVA: normalization and evaluation of MS-based metabolomics data. Nucleic Acids Research (impact factor of the publication year: 10.162, 生物一区 TOP 期刊). 45(W1): 162-170 (2017).  
  5. ESI Highly Cited Paper:
    • The Percentile in Subject Area shown in InCites™ was 0.71% in 2021.
    • The Percentile in Subject Area shown in InCites™ was 0.75% in 2020.
    • The Percentile in Subject Area shown in InCites™ was 1.27% in 2019.
    • The Percentile in Subject Area shown in InCites™ was 2.98% in 2018.
    Highlights by Experts in Subject Area:
    • Introduced by OMICTOOLS as "provided valuable guidance to the selection of suitable algorithm in metabolomics".
    • Discussed in StackExchange as "works fine" and "corrections for batches without QC options".

  6. Q. X. Yang, J. J. Hong, Y. Li, W. W. Xue, S. Li*, H. Yang*, F. Zhu*. A novel bioinformatics approach to identify the consistently well-performing normalization strategy for current metabolomic studies. Briefings in Bioinformatics (impact factor of the publication year: 9.101, 生物一区 TOP 期刊). 21(6): 2142-2152 (2020).  
  7. B. Li, J. Tang, Q. X. Yang, X. J. Cui, S. Li, S. J. Chen, Q. X. Cao, W. W. Xue, N. Chen, F. Zhu*. Performance evaluation and online realization of data-driven normalization methods used in LC/MS based untargeted metabolomics analysis. Scientific Reports (impact factor of the publication year: 5.228, 综合性二区期刊). 6: 38881 (2016).
  8. ESI Highly Cited Paper:
    • The Percentile in Subject Area shown in InCites™ was 1.83% in 2021.
    • The Percentile in Subject Area shown in InCites™ was 1.87% in 2020.
    • The Percentile in Subject Area shown in InCites™ was 2.05% in 2019.

  ANPELA: ANalysis and PErformance-assessment of the LAbel-free proteome quantification
    Server URL: https://idrblab.org/anpela/

    Label-free quantification (LFQ) with a specific and sequentially integrated workflow of acquisition technique, quantification tool and processing method has emerged as the popular technique employed in metaproteomic research to provide a comprehensive landscape of the adaptive response of microbes to external stimuli and their interactions with other organisms or host cells. The performance of a specific LFQ workflow is highly dependent on the studied data. Hence, it is essential to discover the most appropriate one for a specific data set. However, it is challenging to perform such discovery due to the large number of possible workflows and the multifaceted nature of the evaluation criteria. Herein, a web server ANPELA (https://idrblab.org/anpela/) was developed and validated as the first tool enabling performance assessment of whole LFQ workflow (collective assessment by five well-established criteria with distinct underlying theories), and it enabled the identification of the optimal LFQ workflow(s) by a comprehensive performance ranking. ANPELA not only automatically detects the diverse formats of data generated by all quantification tools but also provides the most complete set of processing methods among the available web servers and stand-alone tools. Systematic validation using metaproteomic benchmarks revealed ANPELA's capabilities in 1 discovering well-performing workflow(s), (2) enabling assessment from multiple perspectives and (3) validating LFQ accuracy using spiked proteins. ANPELA has a unique ability to evaluate the performance of whole LFQ workflow and enables the discovery of the optimal LFQs by the comprehensive performance ranking of all 560 workflows. Therefore, it has great potential for applications in metaproteomic and other studies requiring LFQ techniques, as many features are shared among proteomic studies.

    Our Publication(s) Describing This Server:

  1. J. Tang, J. B. Fu, Y. X. Wang, B. Li, Y. H. Li, Q. X. Yang, X. J. Cui, J. J. Hong, X. F. Li, Y. Z. Chen, W. W. Xue, F. Zhu*. ANPELA: analysis and performance-assessment of the label-free quantification workflow for metaproteomic studies. Briefings in Bioinformatics (impact factor of the publication year: 9.101, 生物一区 TOP 期刊). 21(2): 621-636 (2020).  
  2. ESI Highly Cited Paper:
    • The Percentile in Subject Area shown in InCites™ was 0.05% in 2021.

  3. J. Tang, J. B. Fu, Y. X. Wang, Y. C. Luo, Q. X. Yang, B. Li, G. Tu, J. J. Hong, X. J. Cui, Y. Z. Chen, L. X. Yao, W. W. Xue, F. Zhu*. Simultaneous improvement in the precision, accuracy and robustness of label-free proteome quantification by optimizing data manipulation chains. Molecular & Cellular Proteomics (impact factor of the publication year: 5.236, 生物二区 TOP 期刊). 18(8): 1683-1699 (2019).  
  4. ESI Highly Cited Paper:
    • The Percentile in Subject Area shown in InCites™ was 0.81% in 2021.
    • The Percentile in Subject Area shown in InCites™ was 0.57% in 2020.

  SSIZER: Determining the Sample Sufficiency for Comparative Biological Study
    Server URL: https://idrblab.org/ssizer/

    Comparative biomedical studies typically require plenty of samples to achieve statistically significant analysis. A frequently-encountered question is how many samples are sufficient for a particular study. This question has been traditionally assessed using the statistical power, but this assessment alone may not guarantee the full and reproducible discovery of markers truly discriminating biological groups (BMC Bioinformatics. 11: 447, 2010; Nat Rev Neurosci. 14: 365-76, 2013). Two novel types of statistical indexes have thus been introduced to assess the sample size from different perspectives by considering the diagnostic accuracy (Metabolomics. 9: 280-99, 2013) and robustness (Cancer Res. 74: 4612-21, 2014). Due to the complementary nature of these index-types, a comprehensive evaluation based on all types of indexes is necessary for more accurate assessment. However, no such tool is available yet. Herein, an online tool SSizer was developed and validated to enable the assessment of the sufficiency of a user-input biomedical dataset for given studies, and three index-types were provided for the first time to achieve the comprehensive assessment. These indexes included: (I) statistical power analyzing the level of difference between two comparative groups (Radiology. 227: 309-13, 2003), (II) overall diagnostic & classification accuracies on independent data (Metabolomics. 9: 280-99, 2013), and (III) robustness among the lists of biomarkers identified from different datasets (Cancer Res. 74:4612-21, 2014). Moreover, a sample simulation based on user-input data was performed to expand data and then determine the sample size required for given study (Anal Chem. 88: 5179-88, 2016). In sum, SSizer was unique for its capacity in comprehensively evaluating whether sample size was sufficient and determining the required number of samples for user-input dataset, which can therefore facilitate current biomedical studies including metabolomics, proteomics, and so on. SSizer is accessible free of charge at https://idrblab.org/ssizer/

    Our Publication(s) Describing This Server:

  1. F. C. Li, Y. Zhou, X. Y. Zhang, J. Tang, Q. X. Yang, Y. Zhang, Y. C. Luo, J. Hu*, W. W. Xue, Y. Q. Qiu, Q. J. He, B. Yang, F. Zhu*. SSizer: determining the sample sufficiency for comparative biological study. Journal of Molecular Biology (impact factor of the publication year: 5.067, 生物二区 TOP 期刊). 432(11): 3411-3421 (2020).  
  CNN-T4SE: CNN-based annotation of bacterial Type IV Secretion system Effectors
    Server URL: https://idrblab.org/cnnt4se/

    The type IV bacterial secretion system (SS) is reported to be one of the most ubiquitous SSs in nature, and can induce serious conditions by secreting type IV SS effectors (T4SEs) into the host cells. Recent studies mainly focus on annotating new T4SE from the huge amount of sequencing data, and various computational tools are therefore developed to accelerate T4SE annotation. However, these tools are reported as heavily dependent on the selected methods and their annotation performance need to be further enhanced. Herein, a convolution neural network (CNN) technique was used to annotate T4SEs by integrating multiple protein encoding strategies. First, the annotation accuracies of nine encoding strategies integrated with CNN were assessed and compared with that of the popular T4SE annotation tools based on independent benchmark. Second, false discovery rates (FDRs) of various models were systematically evaluated by (1) scanning the genome of Legionella pneumophila subsp. ATCC 33152 and (2) predicting the real-world non-T4SEs validated using published experiments. Based on above analyses, the encoding strategies, (a) position-specific scoring matrix (PSSM), (b) protein secondary structure & solvent accessibility (PSSSA) and (c) one-hot encoding scheme (Onehot), were identified as well-performing when integrated CNN. Finally, a novel strategy that collectively considering the three well-performing models (CNN-PSSM, CNN-PSSSA and CNN-Onehot) was proposed, and a new tool (CNN-T4SE, https://idrblab.org/cnnt4se/) was constructed to facilitate T4SE annotation. All in all, this study conducted a comprehensive analysis on the performance of a collection of encoding strategies when integrated with CNN, which could facilitate the suppression of T4SS in infection and limit the spread of antimicrobial resistance.

    Our Publication(s) Describing This Server:

  1. J. J. Hong, Y. C. Luo, M. J. Mou, J. B. Fu, Y. Zhang, W. W. Xue, T. Xie, L. Tao*, Y. Lou*, F. Zhu*. Convolutional neural network-based annotation of bacterial type IV secretion system effectors with enhanced accuracy and reduced false discovery. Briefings in Bioinformatics (impact factor of the publication year: 9.101, 生物一区 TOP 期刊). 21(5): 1825-1836 (2020).  
  PROFEAT: calculation of the PROtein physicochemical FEATures
    Server URL: https://idrblab.org/profeat/

    The studies of biological, disease, and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web servers for computing network descriptors, but many descriptors are not covered, including those used or useful for biological studies. We upgraded the PROFEAT web server http://bidd2.nus.edu.sg/cgi-bin/profeat2016/main.cgi for computing up to 329 network descriptors and protein-protein interaction descriptors. PROFEAT network descriptors comprehensively describe the topological and connectivity characteristics of unweighted (uniform binding constants and molecular levels), edge-weighted (varying binding constants), node-weighted (varying molecular levels), edge-node-weighted (varying binding constants and molecular levels), and directed (oriented processes) networks. The usefulness of the network descriptors is illustrated by the literature-reported studies of the biological networks derived from the genome, interactome, transcriptome, metabolome, and diseasome profiles.

    Our Publication(s) Describing This Server:

  1. H. B. Rao&, F. Zhu&, G. B. Yang, Z. R. Li*, Y. Z. Chen. Update of PROFEAT: a web server for computing structural and physicochemical features of proteins and peptides from amino acid sequences. Nucleic Acids Research (impact factor of the publication year: 7.836, 生物一区 TOP 期刊). 39(W1): 385-390 (2011).  
  SVM-Prot: SVM-based Protein functional family prediction
    Server URL: https://idrblab.org/svmprot/

    Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.

    Our Publication(s) Describing This Server:

  1. Y. H. Li, J. Y. Xu, L. Tao, X. F. Li, S. Li, X. Zeng, S. Y. Chen, P. Zhang, C. Qin, C. Zhang, Z. Chen, F. Zhu*, Y. Z. Chen. SVM-Prot 2016: a web-server for machine learning prediction of protein functional families from sequence irrespective of similarity. PLoS ONE (impact factor of the publication year: 3.234, 生物三区期刊). 11(8): e0155290 (2016).
  2. ESI Highly Cited Paper:
    • The Percentile in Subject Area shown in InCites™ was 1.31% in 2021.
    • The Percentile in Subject Area shown in InCites™ was 1.41% in 2020.

  MMEASE: Meta-Metabolomics by Enhanced Annotation, marker Selection and Enrichment
    Server URL: https://idrblab.org/mmease/

    Large-scale and long-term metabolomic studies have attracted widespread attention in the biomedical studies yet remain challenging despite recent technique progresses. In particular, the ineffective way of experiment integration and limited capacity in metabolite annotation are known issues. Herein, we constructed an online tool MMEASE enabling the integration of multiple analytical experiments with an enhanced metabolite annotation and enrichment analysis (https://idrblab.org/mmease/). MMEASE was unique in capable of (1) integrating multiple analytical blocks; (2) providing enriched annotation for >330 thousands of metabolites; (3) conducting enrichment analysis using various categories/sub-categories. All in all, MMEASE aimed at supplying a comprehensive service for long-term and large-scale metabolomics, which might provide valuable guidance to current biomedical studies.

    Our Publication(s) Describing This Server:

  1. Q. X. Yang, B. Li, S. J. Chen, J. Tang, Y. H. Li, Y. Li, S. Zhang, C. Shi, Y. Zhang, M. J. Mou, W. W. Xue*, F. Zhu*. MMEASE: online meta-analysis of metabolomic data by enhanced metabolite annotation, marker selection and enrichment analysis. Journal of Proteomics (impact factor of the publication year: 4.044, 生物二区期刊). 232: 104023 (2021).  
  MetaFS: performance assessment for biomarker discovery in metaproteomics.
    Server URL: https://idrblab.org/metafs/

    Metaproteomic data suffer from two unavoidable issues: dimensionality and sparsity. Data reduction methods can maximally identify the relevant subset of significant differential features and reduce data redundancy. Feature selection (FS) approaches were often applied to obtain the significant differential subset. So far, a variety of feature selection have been developed for metaproteomic study. However, due to FS’s performance depended heavily on the data characteristics of a given research, the well-suitable feature selection method must be carefully chosen for obtaining the reliable and reproducibly results of analyses. Moreover, it is critical to evaluate the performances of each FS method according to comprehensive criteria, because single criterion is not sufficient to reflect the overall level of the FS method. Therefore, we constructed the online tool named MetaFS, which provided 13 types of FS methods and conduct the comprehensive evaluation on the complex FS methods using four widely accepted and independent criteria. Furthermore, the function and reliability of MetaFS were systematically tested and validated via two case studies. In summary, MetaFS could be a distinguished tool discovering the overall well-performed FS method for selecting the potential biomarkers in microbiome studies. The online tool is freely available at https://idrblab.org/metafs/.

    Our Publication(s) Describing This Server:

  1. J. Tang, M. J. Mou, Y. X. Wang, Y. C. Luo, F. Zhu*. MetaFS: performance assessment of biomarker discovery in metaproteomics. Briefings in Bioinformatics (impact factor of the publication year: 11.622, 生物一区 TOP 期刊). doi: 10.1093/bib/bbaa105 (2021).  
IDRB: Innovative Drug Research and Bioinformatics Group

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College of Pharmaceutical Sciences, Zhejiang University
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