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Mining nematode protein secretomes to explain lifestyle and host specificity.

Lucienne Tritten | Cristina Ballesteros | Robin Beech | Timothy G Geary | Yovany Moreno
PLoS neglected tropical diseases | 2021

Parasitic nematodes are highly successful pathogens, inflicting disease on humans, animals and plants. Despite great differences in their life cycles, host preference and transmission modes, these parasites share a common capacity to manipulate their host's immune system. This is at least partly achieved through the release of excretory/secretory proteins, the most well-characterized component of nematode secretomes, that are comprised of functionally diverse molecules. In this work, we analyzed published protein secretomes of parasitic nematodes to identify common patterns as well as species-specific traits. The 20 selected organisms span 4 nematode clades, including plant pathogens, animal parasites, and the free-living species Caenorhabditis elegans. Transthyretin-like proteins were the only component common to all adult secretomes; many other protein classes overlapped across multiple datasets. The glycolytic enzymes aldolase and enolase were present in all parasitic species, but missing from C. elegans. Secretomes from larval stages showed less overlap between species. Although comparison of secretome composition across species and life-cycle stages is challenged by the use of different methods and depths of sequencing among studies, our workflow enabled the identification of conserved protein families and pinpointed elements that may have evolved as to enable parasitism. This strategy, extended to more secretomes, may be exploited to prioritize therapeutic targets in the future.

Pubmed ID: 34587193

Associated grants

None

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This is a list of tools and resources that we have found mentioned in this publication.


Pfam (tool)

RRID:SCR_004726

A database of protein families, each represented by multiple sequence alignments and hidden Markov models (HMMs). Users can analyze protein sequences for Pfam matches, view Pfam family annotation and alignments, see groups of related families, look at the domain organization of a protein sequence, find the domains on a PDB structure, and query Pfam by keywords. There are two components to Pfam: Pfam-A and Pfam-B. Pfam-A entries are high quality, manually curated families that may automatically generate a supplement using the ADDA database. These automatically generated entries are called Pfam-B. Although of lower quality, Pfam-B families can be useful for identifying functionally conserved regions when no Pfam-A entries are found. Pfam also generates higher-level groupings of related families, known as clans (collections of Pfam-A entries which are related by similarity of sequence, structure or profile-HMM).

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PubMed (tool)

RRID:SCR_004846

Public bibliographic database that provides access to citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. PubMed citations and abstracts include fields of biomedicine and health, covering portions of life sciences, behavioral sciences, chemical sciences, and bioengineering. Provides access to additional relevant web sites and links to other NCBI molecular biology resources. Publishers of journals can submit their citations to NCBI and then provide access to full-text of articles at journal web sites using LinkOut.

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Hmmer (tool)

RRID:SCR_005305

Tool for searching sequence databases for homologs of protein sequences, and for making protein sequence alignments. It implements methods using probabilistic models called profile hidden Markov models (profile HMMs). Compared to BLAST, FASTA, and other sequence alignment and database search tools based on older scoring methodology, HMMER aims to be significantly more accurate and more able to detect remote homologs because of the strength of its underlying mathematical models. In the past, this strength came at significant computational expense, but in the new HMMER3 project, HMMER is now essentially as fast as BLAST.

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Blast2GO (tool)

RRID:SCR_005828

An ALL in ONE tool for functional annotation of (novel) sequences and the analysis of annotation data. Blast2GO (B2G) joins in one universal application similarity search based GO annotation and functional analysis. B2G offers the possibility of direct statistical analysis on gene function information and visualization of relevant functional features on a highlighted GO direct acyclic graph (DAG). Furthermore B2G includes various statistics charts summarizing the results obtained at BLASTing, GO-mapping, annotation and enrichment analysis (Fisher''''s Exact Test). All analysis process steps are configurable and data import and export are supported at any stage. The application also accepts pre-existing BLAST or annotation files and takes them to subsequent steps. The tool offers a very suitable platform for high throughput functional genomics research in non-model species. B2G is a species-independent, intuitive and interactive desktop application which allows monitoring and comprehending the whole annotation and analysis process supported by additional features like GO Slim integration, evidence code (EC) consideration, a Batch-Mode or GO-Multilevel-Pies. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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MAFFT (tool)

RRID:SCR_011811

Software package as multiple alignment program for amino acid or nucleotide sequences. Can align up to 500 sequences or maximum file size of 1 MB. First version of MAFFT used algorithm based on progressive alignment, in which sequences were clustered with help of Fast Fourier Transform. Subsequent versions have added other algorithms and modes of operation, including options for faster alignment of large numbers of sequences, higher accuracy alignments, alignment of non-coding RNA sequences, and addition of new sequences to existing alignments.

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MassLynx (tool)

RRID:SCR_014271

Software which can acquire, analyze, manage, and share mass spectrometry data. MassLynx controls any Waters mass spectrometry system, from sample and solvent management components to mass spectrometer and auxiliary detectors. The software can acquire nominal mass, exact mass, MS/MS and exact mass MS/MS data. The software system also maintains and consolidates all user sample data. Optional Application Manager programs provide additional information for specific MS analyses and data.

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PhyML (tool)

RRID:SCR_014629

Web phylogeny server based on the maximum-likelihood principle.

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SignalP (tool)

RRID:SCR_015644

Web application for prediction of the presence and location of signal peptide cleavage sites in amino acid sequences from different organisms. The method incorporates a prediction of cleavage sites and a signal peptide/non-signal peptide prediction based on a combination of several artificial neural networks.

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OrthoFinder (tool)

RRID:SCR_017118

Software Python application for comparative genomics analysis. Finds orthogroups and orthologs, infers rooted gene trees for all orthogroups and identifies all of gene duplcation events in those gene trees, infers rooted species tree for species being analysed and maps gene duplication events from gene trees to branches in species tree, improves orthogroup inference accuracy. Runs set of protein sequence files, one per species, in FASTA format.

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Exponentially Modified Protein Abundance Index (tool)

RRID:SCR_008616

emPAI (exponentially modified protein abundance index), developed by Ishihama et al., is a measure to describe the protein composition in sample solutions. When the total protein amount in the sample is available, emPAI can be converted to the absolute amount of each protein in the sample. emPAI is derived from PAI, which is defined as the number of the observed peptides divided by the number of the observable peptides per protein. We recently found that log (PAI) had linear relationship to the protein amounts, and that emPAI, 10^(PAI)-1, was proportional to the protein amounts for whole cell lysate digested by trypsin. The accuracy of this method was within factor 5, similar or better than determination of abundance by protein staining

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