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  1. Article ; Online: Incorporating metabolic activity, taxonomy and community structure to improve microbiome-based predictive models for host phenotype prediction.

    Monshizadeh, Mahsa / Ye, Yuzhen

    Gut microbes

    2024  Volume 16, Issue 1, Page(s) 2302076

    Abstract: We developed MicroKPNN, a prior-knowledge guided interpretable neural network for microbiome-based human host phenotype prediction. The prior knowledge used in MicroKPNN includes the metabolic activities of different bacterial species, phylogenetic ... ...

    Abstract We developed MicroKPNN, a prior-knowledge guided interpretable neural network for microbiome-based human host phenotype prediction. The prior knowledge used in MicroKPNN includes the metabolic activities of different bacterial species, phylogenetic relationships, and bacterial community structure, all in a shallow neural network. Application of MicroKPNN to seven gut microbiome datasets (involving five different human diseases including inflammatory bowel disease, type 2 diabetes, liver cirrhosis, colorectal cancer, and obesity) shows that incorporation of the prior knowledge helped improve the microbiome-based host phenotype prediction. MicroKPNN outperformed fully connected neural network-based approaches in all seven cases, with the most improvement of accuracy in the prediction of type 2 diabetes. MicroKPNN outperformed a recently developed deep-learning based approach DeepMicro, which selects the best combination of autoencoder and machine learning approach to make predictions, in all of the seven cases. Importantly, we showed that MicroKPNN provides a way for interpretation of the predictive models. Using importance scores estimated for the hidden nodes, MicroKPNN could provide explanations for prior research findings by highlighting the roles of specific microbiome components in phenotype predictions. In addition, it may suggest potential future research directions for studying the impacts of microbiome on host health and diseases. MicroKPNN is publicly available at https://github.com/mgtools/MicroKPNN.
    MeSH term(s) Humans ; Gastrointestinal Microbiome ; Phylogeny ; Diabetes Mellitus, Type 2/microbiology ; Microbiota/genetics ; Phenotype
    Language English
    Publishing date 2024-01-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2575755-6
    ISSN 1949-0984 ; 1949-0984
    ISSN (online) 1949-0984
    ISSN 1949-0984
    DOI 10.1080/19490976.2024.2302076
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Protein embedding based alignment.

    Iovino, Benjamin Giovanni / Ye, Yuzhen

    BMC bioinformatics

    2024  Volume 25, Issue 1, Page(s) 85

    Abstract: Purpose: Despite the many progresses with alignment algorithms, aligning divergent protein sequences with less than 20-35% pairwise identity (so called "twilight zone") remains a difficult problem. Many alignment algorithms have been using substitution ... ...

    Abstract Purpose: Despite the many progresses with alignment algorithms, aligning divergent protein sequences with less than 20-35% pairwise identity (so called "twilight zone") remains a difficult problem. Many alignment algorithms have been using substitution matrices since their creation in the 1970's to generate alignments, however, these matrices do not work well to score alignments within the twilight zone. We developed Protein Embedding based Alignments, or PEbA, to better align sequences with low pairwise identity. Similar to the traditional Smith-Waterman algorithm, PEbA uses a dynamic programming algorithm but the matching score of amino acids is based on the similarity of their embeddings from a protein language model.
    Methods: We tested PEbA on over twelve thousand benchmark pairwise alignments from BAliBASE, each one extracted from one of their multiple sequence alignments. Five different BAliBASE references were used, each with different sequence identities, motifs, and lengths, allowing PEbA to showcase how well it aligns under different circumstances.
    Results: PEbA greatly outperformed BLOSUM substitution matrix-based pairwise alignments, achieving different levels of improvements of the alignment quality for pairs of sequences with different levels of similarity (over four times as well for pairs of sequences with <10% identity). We also compared PEbA with embeddings generated by different protein language models (ProtT5 and ESM-2) and found that ProtT5-XL-U50 produced the most useful embeddings for aligning protein sequences. PEbA also outperformed DEDAL and vcMSA, two recently developed protein language model embedding-based alignment methods.
    Conclusion: Our results suggested that general purpose protein language models provide useful contextual information for generating more accurate protein alignments than typically used methods.
    MeSH term(s) Proteins/chemistry ; Boronic Acids ; Amino Acid Sequence ; Sequence Alignment ; Algorithms
    Chemical Substances phenylethane boronic acid (34420-17-2) ; Proteins ; Boronic Acids
    Language English
    Publishing date 2024-02-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041484-5
    ISSN 1471-2105 ; 1471-2105
    ISSN (online) 1471-2105
    ISSN 1471-2105
    DOI 10.1186/s12859-024-05699-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Meta-analysis of microbiome association networks reveal patterns of dysbiosis in diseased microbiomes.

    Lam, Tony J / Ye, Yuzhen

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 17482

    Abstract: The human gut microbiome is composed of a diverse and dynamic population of microbial species which play key roles in modulating host health and physiology. While individual microbial species have been found to be associated with certain disease states, ... ...

    Abstract The human gut microbiome is composed of a diverse and dynamic population of microbial species which play key roles in modulating host health and physiology. While individual microbial species have been found to be associated with certain disease states, increasing evidence suggests that higher-order microbial interactions may have an equal or greater contribution to host fitness. To better understand microbial community dynamics, we utilize networks to study interactions through a meta-analysis of microbial association networks between healthy and disease gut microbiomes. Taking advantage of the large number of metagenomes derived from healthy individuals and patients with various diseases, together with recent advances in network inference that can deal with sparse compositional data, we inferred microbial association networks based on co-occurrence of gut microbial species and made the networks publicly available as a resource (GitHub repository named GutNet). Through our meta-analysis of inferred networks, we were able to identify network-associated features that help stratify between healthy and disease states such as the differentiation of various bacterial phyla and enrichment of Proteobacteria interactions in diseased networks. Additionally, our findings show that the contributions of taxa in microbial associations are disproportionate to their abundances and that rarer taxa of microbial species play an integral part in shaping dynamics of microbial community interactions. Network-based meta-analysis revealed valuable insights into microbial community dynamics between healthy and disease phenotypes. We anticipate that the healthy and diseased microbiome association networks we inferred will become an important resource for human-related microbiome research.
    MeSH term(s) Humans ; Dysbiosis/microbiology ; Microbiota/genetics ; Gastrointestinal Microbiome/genetics ; Metagenome ; Microbial Interactions
    Language English
    Publishing date 2022-10-19
    Publishing country England
    Document type Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-22541-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: MetaProD: A Highly-Configurable Mass Spectrometry Analyzer for Multiplexed Proteomic and Metaproteomic Data.

    Canderan, Jamie / Stamboulian, Moses / Ye, Yuzhen

    Journal of proteome research

    2023  Volume 22, Issue 2, Page(s) 442–453

    Abstract: The microbiome has been shown to be important for human health because of its influence on disease and the immune response. Mass spectrometry is an important tool for evaluating protein expression and species composition in the microbiome but is ... ...

    Abstract The microbiome has been shown to be important for human health because of its influence on disease and the immune response. Mass spectrometry is an important tool for evaluating protein expression and species composition in the microbiome but is technically challenging and time-consuming. Multiplexing has emerged as a way to make spectrometry workflows faster while improving results. Here, we present MetaProD (MetaProteomics in Django) as a highly configurable metaproteomic data analysis pipeline supporting label-free and multiplexed mass spectrometry. The pipeline is open-source, uses fully open-source tools, and is integrated with Django to offer a web-based interface for configuration and data access. Benchmarking of MetaProD using multiple metaproteomics data sets showed that MetaProD achieved fast and efficient identification of peptides and proteins. Application of MetaProD to a multiplexed cancer data set resulted in identification of more differentially expressed human proteins in cancer tissues versus healthy tissues as compared to previous studies; in addition, MetaProD identified bacterial proteins in those samples, some of which are differentially abundant.
    MeSH term(s) Humans ; Proteomics/methods ; Microbiota ; Mass Spectrometry ; Bacterial Proteins ; Spectrum Analysis
    Chemical Substances Bacterial Proteins
    Language English
    Publishing date 2023-01-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.2c00614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Accurate de novo peptide sequencing using fully convolutional neural networks

    Kaiyuan Liu / Yuzhen Ye / Sujun Li / Haixu Tang

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 11

    Abstract: Abstract De novo peptide sequencing, which does not rely on a comprehensive target sequence database, provides us with a way to identify novel peptides from tandem mass spectra. However, current de novo sequencing algorithms suffer from low accuracy and ... ...

    Abstract Abstract De novo peptide sequencing, which does not rely on a comprehensive target sequence database, provides us with a way to identify novel peptides from tandem mass spectra. However, current de novo sequencing algorithms suffer from low accuracy and coverage, which hinders their application in proteomics. In this paper, we present PepNet, a fully convolutional neural network for high accuracy de novo peptide sequencing. PepNet takes an MS/MS spectrum (represented as a high-dimensional vector) as input, and outputs the optimal peptide sequence along with its confidence score. The PepNet model is trained using a total of 3 million high-energy collisional dissociation MS/MS spectra from multiple human peptide spectral libraries. Evaluation results show that PepNet significantly outperforms current best-performing de novo sequencing algorithms (e.g. PointNovo and DeepNovo) in both peptide-level accuracy and positional-level accuracy. PepNet can sequence a large fraction of spectra that were not identified by database search engines, and thus could be used as a complementary tool to database search engines for peptide identification in proteomics. In addition, PepNet runs around 3x and 7x faster than PointNovo and DeepNovo on GPUs, respectively, thus being more suitable for the analysis of large-scale proteomics data.
    Keywords Science ; Q
    Subject code 006
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Accurate de novo peptide sequencing using fully convolutional neural networks.

    Liu, Kaiyuan / Ye, Yuzhen / Li, Sujun / Tang, Haixu

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 7974

    Abstract: De novo peptide sequencing, which does not rely on a comprehensive target sequence database, provides us with a way to identify novel peptides from tandem mass spectra. However, current de novo sequencing algorithms suffer from low accuracy and coverage, ...

    Abstract De novo peptide sequencing, which does not rely on a comprehensive target sequence database, provides us with a way to identify novel peptides from tandem mass spectra. However, current de novo sequencing algorithms suffer from low accuracy and coverage, which hinders their application in proteomics. In this paper, we present PepNet, a fully convolutional neural network for high accuracy de novo peptide sequencing. PepNet takes an MS/MS spectrum (represented as a high-dimensional vector) as input, and outputs the optimal peptide sequence along with its confidence score. The PepNet model is trained using a total of 3 million high-energy collisional dissociation MS/MS spectra from multiple human peptide spectral libraries. Evaluation results show that PepNet significantly outperforms current best-performing de novo sequencing algorithms (e.g. PointNovo and DeepNovo) in both peptide-level accuracy and positional-level accuracy. PepNet can sequence a large fraction of spectra that were not identified by database search engines, and thus could be used as a complementary tool to database search engines for peptide identification in proteomics. In addition, PepNet runs around 3x and 7x faster than PointNovo and DeepNovo on GPUs, respectively, thus being more suitable for the analysis of large-scale proteomics data.
    MeSH term(s) Humans ; Tandem Mass Spectrometry/methods ; Sequence Analysis, Protein/methods ; Peptides ; Amino Acid Sequence ; Neural Networks, Computer ; Algorithms ; Peptide Library
    Chemical Substances Peptides ; Peptide Library
    Language English
    Publishing date 2023-12-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-43010-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Identification and classification of reverse transcriptases in bacterial genomes and metagenomes.

    Sharifi, Fatemeh / Ye, Yuzhen

    Nucleic acids research

    2021  Volume 50, Issue 5, Page(s) e29

    Abstract: Reverse transcriptases (RTs) are found in different systems including group II introns, Diversity Generating Retroelements (DGRs), retrons, CRISPR-Cas systems, and Abortive Infection (Abi) systems in prokaryotes. Different classes of RTs can play ... ...

    Abstract Reverse transcriptases (RTs) are found in different systems including group II introns, Diversity Generating Retroelements (DGRs), retrons, CRISPR-Cas systems, and Abortive Infection (Abi) systems in prokaryotes. Different classes of RTs can play different roles, such as template switching and mobility in group II introns, spacer acquisition in CRISPR-Cas systems, mutagenic retrohoming in DGRs, programmed cell suicide in Abi systems, and recently discovered phage defense in retrons. While some classes of RTs have been studied extensively, others remain to be characterized. There is a lack of computational tools for identifying and characterizing various classes of RTs. In this study, we built a tool (called myRT) for identification and classification of prokaryotic RTs. In addition, our tool provides information about the genomic neighborhood of each RT, providing potential functional clues. We applied our tool to predict RTs in all complete and draft bacterial genomes, and created a collection that can be used for exploration of putative RTs and their associated protein domains. Application of myRT to metagenomes showed that gut metagenomes encode proportionally more RTs related to DGRs, outnumbering retron-related RTs, as compared to the collection of reference genomes. MyRT is both available as a standalone software (https://github.com/mgtools/myRT) and also through a website (https://omics.informatics.indiana.edu/myRT/).
    MeSH term(s) Bacteriophages/genetics ; Genome, Bacterial ; Humans ; Metagenome ; RNA-Directed DNA Polymerase/metabolism ; Retroelements/genetics
    Chemical Substances Retroelements ; RNA-Directed DNA Polymerase (EC 2.7.7.49)
    Language English
    Publishing date 2021-12-14
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkab1207
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Comparison of CRISPR-Cas Immune Systems in Healthcare-Related Pathogens.

    Mortensen, Kate / Lam, Tony J / Ye, Yuzhen

    Frontiers in microbiology

    2021  Volume 12, Page(s) 758782

    Abstract: The ESKAPE pathogens ( ...

    Abstract The ESKAPE pathogens (
    Language English
    Publishing date 2021-10-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2021.758782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Locality-Sensitive Hashing-Based k-Mer Clustering for Identification of Differential Microbial Markers Related to Host Phenotype.

    Han, Wontack / Tang, Haixu / Ye, Yuzhen

    Journal of computational biology : a journal of computational molecular cell biology

    2022  Volume 29, Issue 7, Page(s) 738–751

    Abstract: Microbial organisms play important roles in many aspects of human health and diseases. Encouraged by the numerous studies that show the association between microbiomes and human diseases, computational and machine learning methods have been recently ... ...

    Abstract Microbial organisms play important roles in many aspects of human health and diseases. Encouraged by the numerous studies that show the association between microbiomes and human diseases, computational and machine learning methods have been recently developed to generate and utilize microbiome features for prediction of host phenotypes such as disease versus healthy cancer immunotherapy responder versus nonresponder. We have previously developed a
    MeSH term(s) Cluster Analysis ; Metagenome ; Metagenomics/methods ; Microbiota/genetics ; Phenotype
    Language English
    Publishing date 2022-05-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2030900-4
    ISSN 1557-8666 ; 1066-5277
    ISSN (online) 1557-8666
    ISSN 1066-5277
    DOI 10.1089/cmb.2021.0640
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Metaproteomics as a tool for studying the protein landscape of human-gut bacterial species.

    Moses Stamboulian / Jamie Canderan / Yuzhen Ye

    PLoS Computational Biology, Vol 18, Iss 3, p e

    2022  Volume 1009397

    Abstract: Host-microbiome interactions and the microbial community have broad impact in human health and diseases. Most microbiome based studies are performed at the genome level based on next-generation sequencing techniques, but metaproteomics is emerging as a ... ...

    Abstract Host-microbiome interactions and the microbial community have broad impact in human health and diseases. Most microbiome based studies are performed at the genome level based on next-generation sequencing techniques, but metaproteomics is emerging as a powerful technique to study microbiome functional activity by characterizing the complex and dynamic composition of microbial proteins. We conducted a large-scale survey of human gut microbiome metaproteomic data to identify generalist species that are ubiquitously expressed across all samples and specialists that are highly expressed in a small subset of samples associated with a certain phenotype. We were able to utilize the metaproteomic mass spectrometry data to reveal the protein landscapes of these species, which enables the characterization of the expression levels of proteins of different functions and underlying regulatory mechanisms, such as operons. Finally, we were able to recover a large number of open reading frames (ORFs) with spectral support, which were missed by de novo protein-coding gene predictors. We showed that a majority of the rescued ORFs overlapped with de novo predicted protein-coding genes, but on opposite strands or in different frames. Together, these demonstrate applications of metaproteomics for the characterization of important gut bacterial species.
    Keywords Biology (General) ; QH301-705.5
    Subject code 500
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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