Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites

Abstract Accurate species identification and abundance estimation are critical for the interpretation of whole metagenome sequencing (WMS) data. Yet, existing metagenomic profilers suffer from false-positive identifications, which can account for more than 90% of total identified species. Here, by l...

Full description

Bibliographic Details
Main Authors: Zheng Sun, Jiang Liu, Meng Zhang, Tong Wang, Shi Huang, Scott T. Weiss, Yang-Yu Liu
Format: Article
Language:English
Published: Nature Portfolio 2023-09-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-41099-8
_version_ 1797558677753823232
author Zheng Sun
Jiang Liu
Meng Zhang
Tong Wang
Shi Huang
Scott T. Weiss
Yang-Yu Liu
author_facet Zheng Sun
Jiang Liu
Meng Zhang
Tong Wang
Shi Huang
Scott T. Weiss
Yang-Yu Liu
author_sort Zheng Sun
collection DOAJ
description Abstract Accurate species identification and abundance estimation are critical for the interpretation of whole metagenome sequencing (WMS) data. Yet, existing metagenomic profilers suffer from false-positive identifications, which can account for more than 90% of total identified species. Here, by leveraging species-specific Type IIB restriction endonuclease digestion sites as reference instead of universal markers or whole microbial genomes, we present a metagenomic profiler, MAP2B (MetAgenomic Profiler based on type IIB restriction sites), to resolve those issues. We first illustrate the pitfalls of using relative abundance as the only feature in determining false positives. We then propose a feature set to distinguish false positives from true positives, and using simulated metagenomes from CAMI2, we establish a false-positive recognition model. By benchmarking the performance in metagenomic profiling using a simulation dataset with varying sequencing depth and species richness, we illustrate the superior performance of MAP2B over existing metagenomic profilers in species identification. We further test the performance of MAP2B using real WMS data from an ATCC mock community, confirming its superior precision against sequencing depth. Finally, by leveraging WMS data from an IBD cohort, we demonstrate the taxonomic features generated by MAP2B can better discriminate IBD and predict metabolomic profiles.
first_indexed 2024-03-10T17:34:33Z
format Article
id doaj.art-b736b1a77338408e8d70c8868c613de4
institution Directory Open Access Journal
issn 2041-1723
language English
last_indexed 2024-03-10T17:34:33Z
publishDate 2023-09-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj.art-b736b1a77338408e8d70c8868c613de42023-11-20T09:54:50ZengNature PortfolioNature Communications2041-17232023-09-0114111210.1038/s41467-023-41099-8Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sitesZheng Sun0Jiang Liu1Meng Zhang2Tong Wang3Shi Huang4Scott T. Weiss5Yang-Yu Liu6Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolQingdao OE Biotechnology Company LimitedKey Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural UniversityChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolFaculty of Dentistry, The University of Hong KongChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical SchoolAbstract Accurate species identification and abundance estimation are critical for the interpretation of whole metagenome sequencing (WMS) data. Yet, existing metagenomic profilers suffer from false-positive identifications, which can account for more than 90% of total identified species. Here, by leveraging species-specific Type IIB restriction endonuclease digestion sites as reference instead of universal markers or whole microbial genomes, we present a metagenomic profiler, MAP2B (MetAgenomic Profiler based on type IIB restriction sites), to resolve those issues. We first illustrate the pitfalls of using relative abundance as the only feature in determining false positives. We then propose a feature set to distinguish false positives from true positives, and using simulated metagenomes from CAMI2, we establish a false-positive recognition model. By benchmarking the performance in metagenomic profiling using a simulation dataset with varying sequencing depth and species richness, we illustrate the superior performance of MAP2B over existing metagenomic profilers in species identification. We further test the performance of MAP2B using real WMS data from an ATCC mock community, confirming its superior precision against sequencing depth. Finally, by leveraging WMS data from an IBD cohort, we demonstrate the taxonomic features generated by MAP2B can better discriminate IBD and predict metabolomic profiles.https://doi.org/10.1038/s41467-023-41099-8
spellingShingle Zheng Sun
Jiang Liu
Meng Zhang
Tong Wang
Shi Huang
Scott T. Weiss
Yang-Yu Liu
Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites
Nature Communications
title Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites
title_full Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites
title_fullStr Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites
title_full_unstemmed Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites
title_short Removal of false positives in metagenomics-based taxonomy profiling via targeting Type IIB restriction sites
title_sort removal of false positives in metagenomics based taxonomy profiling via targeting type iib restriction sites
url https://doi.org/10.1038/s41467-023-41099-8
work_keys_str_mv AT zhengsun removaloffalsepositivesinmetagenomicsbasedtaxonomyprofilingviatargetingtypeiibrestrictionsites
AT jiangliu removaloffalsepositivesinmetagenomicsbasedtaxonomyprofilingviatargetingtypeiibrestrictionsites
AT mengzhang removaloffalsepositivesinmetagenomicsbasedtaxonomyprofilingviatargetingtypeiibrestrictionsites
AT tongwang removaloffalsepositivesinmetagenomicsbasedtaxonomyprofilingviatargetingtypeiibrestrictionsites
AT shihuang removaloffalsepositivesinmetagenomicsbasedtaxonomyprofilingviatargetingtypeiibrestrictionsites
AT scotttweiss removaloffalsepositivesinmetagenomicsbasedtaxonomyprofilingviatargetingtypeiibrestrictionsites
AT yangyuliu removaloffalsepositivesinmetagenomicsbasedtaxonomyprofilingviatargetingtypeiibrestrictionsites