StrainPanDA: Linked reconstruction of strain composition and gene content profiles via pangenome‐based decomposition of metagenomic data

Hu, Han; Tan, Yuxiang; Li, Chenhao; Chen, Junyu; Kou, Yan; Xu, Zhenjiang; Liu, Yang‐Yu; Tan, Yan; Dai, Lei

doi:10.1002/imt2.41

Cited by 11 publications

(9 citation statements)

References 91 publications

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“…Some species are represented by more than one strain (marker shape). (C) Accuracy of gene content estimates by StrainPGC (y-axis) compared to PanPhlAn [@Beghini2021] and StrainPanDA [@Hu2022] (x-axes), as measured by precision, recall, and F1. All three indices range between 0 and 1, and higher values reflect better performance.…”

Section: Resultsmentioning

confidence: 99%

“…We next compared StrainPGC’s performance to two alternative, state-of-the-art methods: PanPhlAn [@Beghini2021], which is widely used and operates on single samples, and StrainPanDA [@Hu2022], a recently published tool that harnesses information across multiple samples and applies non-negative matrix factorization to jointly estimate gene content and strain depth (Fig. 2C).…”

Section: Resultsmentioning

confidence: 99%

“…In order to minimize the impacts of inter- and intra-specific cross-mapping on pangenome profiling, which can be major problems for gene databases constructed with MAGs, we made major changes to the clustering and curation pipeline. In this MIDAS update, described below, we sought to minimize the impact of fragmented gene sequences, spurious gene calls, chimeric assemblies, and redundant OGFs resulting from these errors [@Li2022;@Hyatt2012;@Dimonaco2022].…”

Section: Methodsmentioning

confidence: 99%

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Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC

Smith,

Zhao,

Dubinkina

et al. 2024

Preprint

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Metagenomics has greatly expanded our understanding of the gut microbiome by revealing vast diversity within and across human hosts. Even within a single species, different strains can have highly divergent gene content, affecting traits such as antibiotic resistance, metabolism, and virulence. Methods that harness metagenomic data to resolve strain-level differences in functional potential are crucial for understanding the causes and consequences of this intraspecific diversity. The enormous size of pangenome references, strain mixing within samples, and inconsistent sequencing depth present challenges for existing tools that analyze samples one at a time. To address this gap, we updated the MIDAS pangenome profiler and developed StrainPGC, an approach to strain-specific gene content estimation that combines strain tracking and correlations across multiple samples. We validate our tool using a synthetic community and find that it outperforms existing approaches. Analyzing a large, publicly available metagenome collection from inflammatory bowel disease patients and healthy controls, we catalog the functional repertoires of thousands of strains across hundreds of species, capturing extensive diversity missing from reference databases. Finally, we apply StrainPGC to metagenomes from a clinical trial of fecal microbiota transplantation for the treatment of ulcerative colitis. We identify two Escherichia coli strains from two different donors that are both frequently transmitted to patients, but have notable differences in functional potential. StrainPGC and MIDAS v3 together enable precise, intraspecific pangenomic investigations using large collections of metagenomic data without microbial isolation or de novo assembly.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC

Smith,

Zhao,

Dubinkina

et al. 2024

Preprint

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“…Our study has several limitations. First, we did not account for potential variations at the strain level (72). Previous studies have shown that the strength of interspecies interactions can vary across different strains, such as the inhibition of Klebsiella pneumoniae by Klebsiella oxytoca (16,73).…”

Section: Discussionmentioning

confidence: 99%

Data-driven prediction of colonization outcomes for complex microbial communities

Wang

Tao

Wang

et al. 2023

Preprint

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Complex microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse physical, biochemical, and ecological processes governing microbial dynamics. Here, we proposed a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validated this approach using synthetic data, finding that machine learning models (including Random Forest and neural ODE) can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conducted colonization experiments for two commensal gut bacteria speciesEnterococcus faeciumandAkkermansia muciniphilain hundreds of human stool-derivedin vitromicrobial communities, confirming that the data-driven approach can successfully predict the colonization outcomes. Furthermore, we found that while most resident species were predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g., the presence ofEnterococcus faecalisinhibits the invasion ofE. faecium. The presented results suggest that the data-driven approach is a powerful tool to inform the ecology and management of complex microbial communities.

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“…Previous studies have detected probiotics in the vagina using qPCR (Cohen et al, 2020) and 16s rRNA amplicon sequencing (Martoni et al, 2022), but these methods cannot provide strain-specific abundance information, so the conclusions are unreliable. In recent years, strain identification methods based on metagenome sequencing data have emerged, such as MetaMp (Dilthey et al, 2019), which uses longread sequencing technology for strain-level annotation, PStrain (Wang et al, 2020), based on single nucleotide variants (SNVs), and StrainPanDA (Hu et al, 2022) that uses pangenome. These advanced methods can provide a more accurate quantitative detection of probiotic colonization and can give direct evidence of the mechanism of action of orally administered probiotics in vivo.…”

Section: Discussionmentioning

confidence: 99%

Orally administratedLactobacillus gasseriTM13 andLactobacillus crispatusLG55 Can Restore the Vaginal Health of Patients Recovering from Bacterial Vaginosis

Fan

Fang

et al. 2022

Preprint

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Bacterial vaginosis (BV) is a common infection of the lower genital tract with a vaginal microbiome dysbiosis caused by decreasing of lactobacilli. Previous studies suggested that supplementation with live Lactobacillus may benefit the recovery of BV, while the outcomes vary in people from different regions. Herein, we aim to evaluate the effectiveness of oral Chinese-origin Lactobacillus with adjuvant metronidazole (MET) on treating Chinese BV patients. In total, 67 Chinese women with BV were enrolled in this parallel controlled trial and randomly assigned to two study groups: a control group treated with MET vaginal suppositories for 7 days and a probiotic group treated with oral Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 as an adjuvant to MET for 30 days. By comparing the participants with Nugent scores ≥ 7 and < 7 on days 14, 30, and 90, we found that oral administration of probiotics did not improve BV cure rates (57.14% and 67.74% at day 14, 57.14% and 58.06% at day 30, 32.14% and 48.39% at day 90 for probiotic and control group respectively). However, the probiotics were effective in restoring vaginal health after cure by showing higher proportion of participants with Nugent scores < 4 in the probiotic group compared to the control group (87.50% and 71.43% on day 14, 93.75% and 88.89% on day 30, and 77.78% and 66.67% on day 90). The relative abundance of the probiotic strains was significantly increased in the gut microbiome of the probiotic group compared to the control group at day 14, but no significance was detected after 30 and 90 days. Also, the probiotics were not detected in vaginal microbiome, suggesting that L. gasseri TM13 and L. crispatus LG55 mainly acted through the gut. A higher abundance of Prevotellatimonensis at baseline was significantly associated with long-term cure failure of BV and greatly contributed to the enrichment of the lipid IVA synthesis pathway, which could aggravate inflammation response. To sum up, L. gasseri TM13 and L. crispatus LG55 can restore the vaginal health of patients recovering from BV, and individualized intervention mode should be developed to improve BV cure rates.

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StrainPanDA: Linked reconstruction of strain composition and gene content profiles via pangenome‐based decomposition of metagenomic data

Cited by 11 publications

References 91 publications

Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC

Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC

Data-driven prediction of colonization outcomes for complex microbial communities

Orally administratedLactobacillus gasseriTM13 andLactobacillus crispatusLG55 Can Restore the Vaginal Health of Patients Recovering from Bacterial Vaginosis

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