Challenges in Bioinformatics Workflows for Processing Microbiome Omics Data at Scale

The nascent field of microbiome science is transitioning from a descriptive approach of cataloging taxa and functions present in an environment to applying multi-omics methods to investigate microbiome dynamics and function. A large number of new tools and algorithms have been designed and used for very specific purposes on samples collected by individual investigators or groups. While these developments have been quite instructive, the ability to compare microbiome data generated by many groups of researchers is impeded by the lack of standardized application of bioinformatics methods. Additionally, there are few examples of broad bioinformatics workflows that can process metagenome, metatranscriptome, metaproteome and metabolomic data at scale, and no central hub that allows processing, or provides varied omics data that are findable, accessible, interoperable and reusable (FAIR). Here, we review some of the challenges that exist in analyzing omics data within the microbiome research sphere, and provide context on how the National Microbiome Data Collaborative has adopted a standardized and open access approach to address such challenges.

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Balances: a new perspective for microbiome analysis

10.1101/219386 ◽

2017 ◽

Cited By ~ 1

Author(s):

J. Rivera-Pinto ◽

J.J. Egozcue ◽

V. Pawlowsky–Glahn ◽

R. Paredes ◽

M. Noguera-Julian ◽

...

Keyword(s):

High Throughput Sequencing ◽

Microbiome Composition ◽

Microbiome Analysis ◽

Microbial Species ◽

Sequencing Technologies ◽

Alternative Approach ◽

Microbiome Research ◽

New Perspective ◽

And Function ◽

Microbiome Data

ABSTRACTHigh-throughput sequencing technologies have revolutionized microbiome research by allowing the relative quantification of microbiome composition and function in different environments. One of the main goals in microbiome analysis is the identification of microbial species that are differentially abundant among groups of samples, or whose abundance is associated with a variable of interest. Most available methods for microbiome abundance testing perform univariate tests for each microbial species or taxa separately, ignoring the compositional nature of microbiome data.We propose an alternative approach for microbiome abundance testing that consists on the identification of two groups of taxa whose relative abundance, or balance, is associated with the response variable of interest. This approach is appealing, since it has direct translation to the biological concept of ecological balance between species in an ecosystem. In this work, we present selbal, a greedy stepwise algorithm for balance selection. We illustrate the algorithm with 16s abundance data from an HIV-microbiome study and a Crohn-microbiome study.ImportanceA more meaningful approach for microbiome abundance testing is presented. Instead of testing each taxon separately we propose to explore abundance balances among groups of taxa. This approach acknowledges the compositional nature of microbiome data.

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Faculty Opinions recommendation of Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1015121.342353 ◽

2005 ◽

Author(s):

Andrea Sant

Keyword(s):

Dendritic Cells ◽

Lymph Node ◽

Langerhans Cells ◽

Dynamics And Function ◽

And Function

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Benchmarking microbiome transformations favors experimental quantitative approaches to address compositionality and sampling depth biases

Nature Communications ◽

10.1038/s41467-021-23821-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Verónica Lloréns-Rico ◽

Sara Vieira-Silva ◽

Pedro J. Gonçalves ◽

Gwen Falony ◽

Jeroen Raes

Keyword(s):

Microbial Communities ◽

Quantitative Methods ◽

Microbial Load ◽

Metagenomic Sequencing ◽

Sampling Depth ◽

Microbiome Research ◽

Microbiome Data ◽

The Impact ◽

Analytical Approaches ◽

Quantitative Approaches

AbstractWhile metagenomic sequencing has become the tool of preference to study host-associated microbial communities, downstream analyses and clinical interpretation of microbiome data remains challenging due to the sparsity and compositionality of sequence matrices. Here, we evaluate both computational and experimental approaches proposed to mitigate the impact of these outstanding issues. Generating fecal metagenomes drawn from simulated microbial communities, we benchmark the performance of thirteen commonly used analytical approaches in terms of diversity estimation, identification of taxon-taxon associations, and assessment of taxon-metadata correlations under the challenge of varying microbial ecosystem loads. We find quantitative approaches including experimental procedures to incorporate microbial load variation in downstream analyses to perform significantly better than computational strategies designed to mitigate data compositionality and sparsity, not only improving the identification of true positive associations, but also reducing false positive detection. When analyzing simulated scenarios of low microbial load dysbiosis as observed in inflammatory pathologies, quantitative methods correcting for sampling depth show higher precision compared to uncorrected scaling. Overall, our findings advocate for a wider adoption of experimental quantitative approaches in microbiome research, yet also suggest preferred transformations for specific cases where determination of microbial load of samples is not feasible.

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Correlating polymer structure, dynamics, and function with atomic force microscopy

Journal of Polymer Science ◽

10.1002/pol.20210321 ◽

2021 ◽

Author(s):

Julia G. Murphy ◽

Jonathan G. Raybin ◽

Steven J. Sibener

Keyword(s):

Atomic Force Microscopy ◽

Polymer Structure ◽

Force Microscopy ◽

Structure Dynamics ◽

Atomic Force ◽

Dynamics And Function ◽

And Function

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Exploring the microbiome in health and disease

Toxicology Research and Application ◽

10.1177/2397847317741884 ◽

2017 ◽

Vol 1 ◽

pp. 239784731774188 ◽

Cited By ~ 5

Author(s):

Elena Scotti ◽

Stéphanie Boué ◽

Giuseppe Lo Sasso ◽

Filippo Zanetti ◽

Vincenzo Belcastro ◽

...

Keyword(s):

Human Health ◽

Metabolic Diseases ◽

Skin Diseases ◽

Human Microbiome ◽

Chronic Obstructive ◽

Microbial Composition ◽

Obstructive Pulmonary Disease ◽

New Findings ◽

Dynamics And Function ◽

And Function

The analysis of human microbiome is an exciting and rapidly expanding field of research. In the past decade, the biological relevance of the microbiome for human health has become evident. Microbiome comprises a complex collection of microorganisms, with their genes and metabolites, colonizing different body niches. It is now well known that the microbiome interacts with its host, assisting in the bioconversion of nutrients and detoxification, supporting immunity, protecting against pathogenic microbes, and maintaining health. Remarkable new findings showed that our microbiome not only primarily affects the health and function of the gastrointestinal tract but also has a strong influence on general body health through its close interaction with the nervous system and the lung. Therefore, a perfect and sensitive balanced interaction of microbes with the host is required for a healthy body. In fact, growing evidence suggests that the dynamics and function of the indigenous microbiota can be influenced by many factors, including genetics, diet, age, and toxicological agents like cigarette smoke, environmental contaminants, and drugs. The disruption of this balance, that is called dysbiosis, is associated with a plethora of diseases, including metabolic diseases, inflammatory bowel disease, chronic obstructive pulmonary disease, periodontitis, skin diseases, and neurological disorders. The importance of the host microbiome for the human health has also led to the emergence of novel therapeutic approaches focused on the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful roles. In the present review, we outline recent studies devoted to elucidate not only the role of microbiome in health conditions and the possible link with various types of diseases but also the influence of various toxicological factors on the microbial composition and function.

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Critical requirement of SOS1 RAS-GEF function for mitochondrial dynamics, metabolism, and redox homeostasis

Oncogene ◽

10.1038/s41388-021-01886-3 ◽

2021 ◽

Author(s):

Rósula García-Navas ◽

Pilar Liceras-Boillos ◽

Carmela Gómez ◽

Fernando C. Baltanás ◽

Nuria Calzada ◽

...

Keyword(s):

Mitochondrial Dynamics ◽

Redox Homeostasis ◽

Atp Production ◽

Oxidative Energy Metabolism ◽

Ras Activation ◽

Mitochondrial Defects ◽

Critical Requirement ◽

Dynamics And Function ◽

And Function ◽

And Control

AbstractSOS1 ablation causes specific defective phenotypes in MEFs including increased levels of intracellular ROS. We showed that the mitochondria-targeted antioxidant MitoTEMPO restores normal endogenous ROS levels, suggesting predominant involvement of mitochondria in generation of this defective SOS1-dependent phenotype. The absence of SOS1 caused specific alterations of mitochondrial shape, mass, and dynamics accompanied by higher percentage of dysfunctional mitochondria and lower rates of electron transport in comparison to WT or SOS2-KO counterparts. SOS1-deficient MEFs also exhibited specific alterations of respiratory complexes and their assembly into mitochondrial supercomplexes and consistently reduced rates of respiration, glycolysis, and ATP production, together with distinctive patterns of substrate preference for oxidative energy metabolism and dependence on glucose for survival. RASless cells showed defective respiratory/metabolic phenotypes reminiscent of those of SOS1-deficient MEFs, suggesting that the mitochondrial defects of these cells are mechanistically linked to the absence of SOS1-GEF activity on cellular RAS targets. Our observations provide a direct mechanistic link between SOS1 and control of cellular oxidative stress and suggest that SOS1-mediated RAS activation is required for correct mitochondrial dynamics and function.

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Dynamics and function of compact nucleosome arrays

Nature Structural & Molecular Biology ◽

10.1038/nsmb.1650 ◽

2009 ◽

Vol 16 (9) ◽

pp. 938-944 ◽

Cited By ~ 88

Author(s):

Michael G Poirier ◽

Eugene Oh ◽

Hannah S Tims ◽

Jonathan Widom

Keyword(s):

Dynamics And Function ◽

And Function ◽

Nucleosome Arrays

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Dynamics and mechanism of ultrafast water–protein interactions

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1602916113 ◽

2016 ◽

Vol 113 (30) ◽

pp. 8424-8429 ◽

Cited By ~ 77

Author(s):

Yangzhong Qin ◽

Lijuan Wang ◽

Dongping Zhong

Keyword(s):

Protein Interactions ◽

Hydration Shell ◽

Water Dynamics ◽

Side Chain ◽

Water Molecules ◽

Ultrafast Dynamics ◽

Hydration Water ◽

Water Side ◽

Dynamics And Function ◽

And Function

Protein hydration is essential to its structure, dynamics, and function, but water–protein interactions have not been directly observed in real time at physiological temperature to our awareness. By using a tryptophan scan with femtosecond spectroscopy, we simultaneously measured the hydration water dynamics and protein side-chain motions with temperature dependence. We observed the heterogeneous hydration dynamics around the global protein surface with two types of coupled motions, collective water/side-chain reorientation in a few picoseconds and cooperative water/side-chain restructuring in tens of picoseconds. The ultrafast dynamics in hundreds of femtoseconds is from the outer-layer, bulk-type mobile water molecules in the hydration shell. We also found that the hydration water dynamics are always faster than protein side-chain relaxations but with the same energy barriers, indicating hydration shell fluctuations driving protein side-chain motions on the picosecond time scales and thus elucidating their ultimate relationship.

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