Dataset Information

GeneRFinder: gene finding in distinct metagenomic data complexities.

ABSTRACT:

Background

Microbes perform a fundamental economic, social, and environmental role in our society. Metagenomics makes it possible to investigate microbes in their natural environments (the complex communities) and their interactions. The way they act is usually estimated by looking at the functions they play in those environments and their responsibility is measured by their genes. The advances of next-generation sequencing technology have facilitated metagenomics research however it also creates a heavy computational burden. Large and complex biological datasets are available as never before. There are many gene predictors available that can aid the gene annotation process though they lack handling appropriately metagenomic data complexities. There is no standard metagenomic benchmark data for gene prediction. Thus, gene predictors may inflate their results by obfuscating low false discovery rates.

Results

We introduce geneRFinder, an ML-based gene predictor able to outperform state-of-the-art gene prediction tools across this benchmark by using only one pre-trained Random Forest model. Average prediction rates of geneRFinder differed in percentage terms by 54% and 64%, respectively, against Prodigal and FragGeneScan while handling high complexity metagenomes. The specificity rate of geneRFinder had the largest distance against FragGeneScan, 79 percentage points, and 66 more than Prodigal. According to McNemar's test, all percentual differences between predictors performances are statistically significant for all datasets with a 99% confidence interval.

Conclusions

We provide geneRFinder, an approach for gene prediction in distinct metagenomic complexities, available at gitlab.com/r.lorenna/generfinder and https://osf.io/w2yd6/ , and also we provide a novel, comprehensive benchmark data for gene prediction-which is based on The Critical Assessment of Metagenome Interpretation (CAMI) challenge, and contains labeled data from gene regions-available at https://sourceforge.net/p/generfinder-benchmark .

SUBMITTER: Silva R

PROVIDER: S-EPMC7905635 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

geneRFinder: gene finding in distinct metagenomic data complexities.

Silva Raíssa R Padovani Kleber K Góes Fabiana F Alves Ronnie R

BMC bioinformatics 20210225 1

<h4>Background</h4>Microbes perform a fundamental economic, social, and environmental role in our society. Metagenomics makes it possible to investigate microbes in their natural environments (the complex communities) and their interactions. The way they act is usually estimated by looking at the functions they play in those environments and their responsibility is measured by their genes. The advances of next-generation sequencing technology have facilitated metagenomics research however it als ...[more]

PMID: 33632132

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Project description:BACKGROUND:In shotgun metagenomics, microbial communities are studied through direct sequencing of DNA without any prior cultivation. By comparing gene abundances estimated from the generated sequencing reads, functional differences between the communities can be identified. However, gene abundance data is affected by high levels of systematic variability, which can greatly reduce the statistical power and introduce false positives. Normalization, which is the process where systematic variability is identified and removed, is therefore a vital part of the data analysis. A wide range of normalization methods for high-dimensional count data has been proposed but their performance on the analysis of shotgun metagenomic data has not been evaluated. RESULTS:Here, we present a systematic evaluation of nine normalization methods for gene abundance data. The methods were evaluated through resampling of three comprehensive datasets, creating a realistic setting that preserved the unique characteristics of metagenomic data. Performance was measured in terms of the methods ability to identify differentially abundant genes (DAGs), correctly calculate unbiased p-values and control the false discovery rate (FDR). Our results showed that the choice of normalization method has a large impact on the end results. When the DAGs were asymmetrically present between the experimental conditions, many normalization methods had a reduced true positive rate (TPR) and a high false positive rate (FPR). The methods trimmed mean of M-values (TMM) and relative log expression (RLE) had the overall highest performance and are therefore recommended for the analysis of gene abundance data. For larger sample sizes, CSS also showed satisfactory performance. CONCLUSIONS:This study emphasizes the importance of selecting a suitable normalization methods in the analysis of data from shotgun metagenomics. Our results also demonstrate that improper methods may result in unacceptably high levels of false positives, which in turn may lead to incorrect or obfuscated biological interpretation.