Publications by authors named "Gajender Aleti"

17 Publications

  • Page 1 of 1

Ion identity molecular networking for mass spectrometry-based metabolomics in the GNPS environment.

Nat Commun 2021 06 22;12(1):3832. Epub 2021 Jun 22.

Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.

Molecular networking connects mass spectra of molecules based on the similarity of their fragmentation patterns. However, during ionization, molecules commonly form multiple ion species with different fragmentation behavior. As a result, the fragmentation spectra of these ion species often remain unconnected in tandem mass spectrometry-based molecular networks, leading to redundant and disconnected sub-networks of the same compound classes. To overcome this bottleneck, we develop Ion Identity Molecular Networking (IIMN) that integrates chromatographic peak shape correlation analysis into molecular networks to connect and collapse different ion species of the same molecule. The new feature relationships improve network connectivity for structurally related molecules, can be used to reveal unknown ion-ligand complexes, enhance annotation within molecular networks, and facilitate the expansion of spectral reference libraries. IIMN is integrated into various open source feature finding tools and the GNPS environment. Moreover, IIMN-based spectral libraries with a broad coverage of ion species are publicly available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23953-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219731PMC
June 2021

Searching for host immune-microbiome mechanisms in obsessive-compulsive disorder: A narrative literature review and future directions.

Neurosci Biobehav Rev 2021 06 24;125:517-534. Epub 2021 Feb 24.

Department of Psychiatry, University of California San Diego, La Jolla, California, United States; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, California, United States.

Obsessive-compulsive disorder (OCD) is disabling and often treatment-refractory. Host immunity and gut microbiota have bidirectional communication with each other and with the brain. Perturbations to this axis have been implicated in neuropsychiatric disorders, but immune-microbiome signaling in OCD is relatively underexplored. We review support for further pursuing such investigations in OCD, including: 1) gut microbiota has been associated with OCD, but causal pathogenic mechanisms remain unclear; 2) early environmental risk factors for OCD overlap with critical periods of immune-microbiome development; 3) OCD is associated with increased risk of immune-mediated disorders and changes in immune parameters, which are separately associated with the microbiome; and 4) gut microbiome manipulations in animal models are associated with changes in immunity and some obsessive-compulsive symptoms. Theoretical pathogenic mechanisms could include microbiota programming of cytokine production, promotion of expansion and trafficking of peripheral immune cells to the CNS, and regulation of microglial function. Immune-microbiome signaling in OCD requires further exploration, and may offer novel insights into pathogenic mechanisms and potential treatment targets for this disabling disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2021.02.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106658PMC
June 2021

Correction to: Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma.

Microb Ecol 2020 Nov 20. Epub 2020 Nov 20.

Department of Genomic Medicine, J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA, 92037, USA.

The original article contained mistakes in the authors' affiliations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00248-020-01641-3DOI Listing
November 2020

Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma.

Microb Ecol 2020 Nov 6. Epub 2020 Nov 6.

Department of Genomic Medicine, J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA, 92037, USA.

The human microbiome has been the focus of numerous research efforts to elucidate the pathogenesis of human diseases including cancer. Oral cancer mortality is high when compared with other cancers, as diagnosis often occurs during late stages. Its prevalence has increased in the USA over the past decade and accounts for over 40,000 new cancer patients each year. Additionally, oral cancer pathogenesis is not fully understood and is likely multifactorial. To unravel the relationships that are associated with the oral microbiome and their virulence factors, we used 16S rDNA and metagenomic sequencing to characterize the microbial composition and functional content in oral squamous cell carcinoma (OSCC) tumor tissue, non-tumor tissue, and saliva from 18 OSCC patients. Results indicate a higher number of bacteria belonging to the Fusobacteria, Bacteroidetes, and Firmicutes phyla associated with tumor tissue when compared with all other sample types. Additionally, saliva metaproteomics revealed a significant increase of Prevotella in five OSCC subjects, while Corynebacterium was mostly associated with ten healthy subjects. Lastly, we determined that there are adhesion and virulence factors associated with Streptococcus gordonii as well as from known oral pathogens belonging to the Fusobacterium genera found mostly in OSCC tissues. From these results, we propose that not only will the methods utilized in this study drastically improve OSCC diagnostics, but the organisms and specific virulence factors from the phyla detected in tumor tissue may be excellent biomarkers for characterizing disease progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00248-020-01596-5DOI Listing
November 2020

ReDU: a framework to find and reanalyze public mass spectrometry data.

Nat Methods 2020 09 17;17(9):901-904. Epub 2020 Aug 17.

Grupo de Investigación en Ciencias Biológicas y Bioprocesos (CIBIOP), Department of Biological Sciences, Universidad EAFIT, Medellín, Colombia.

We present ReDU ( https://redu.ucsd.edu/ ), a system for metadata capture of public mass spectrometry-based metabolomics data, with validated controlled vocabularies. Systematic capture of knowledge enables the reanalysis of public data and/or co-analysis of one's own data. ReDU enables multiple types of analyses, including finding chemicals and associated metadata, comparing the shared and different chemicals between groups of samples, and metadata-filtered, repository-scale molecular networking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41592-020-0916-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968862PMC
September 2020

Differing salivary microbiome diversity, community and diurnal rhythmicity in association with affective state and peripheral inflammation in adults.

Brain Behav Immun 2020 07 14;87:591-602. Epub 2020 Feb 14.

Department of Psychiatry, United States; Center for Microbiome Innovation, United States; Department of Family Medicine and Public Health, University of California, San Diego, United States. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2020.02.004DOI Listing
July 2020

Host-Microbial Interactions in Systemic Lupus Erythematosus and Periodontitis.

Front Immunol 2019 12;10:2602. Epub 2019 Nov 12.

Department of Genomic Medicine, J. Craig Venter Institute, La Jolla, CA, United States.

Systemic lupus erythematosus (SLE) is a potentially fatal complex autoimmune disease, that is characterized by widespread inflammation manifesting tissue damage and comorbidities across the human body including heart, blood vessels, joints, skin, liver, kidneys, and periodontal tissues. The etiology of SLE is partially attributed to a deregulated inflammatory response to microbial dysbiosis and environmental changes. In the mouth, periodontal environment provides an optimal niche for local and systemic inflammation. Our aim was to evaluate the reciprocal impact of periodontal subgingival microbiome on SLE systemic inflammation. Ninety-one female subjects were recruited, including healthy ( = 31), SLE-inactive ( = 29), and SLE-active ( = 31). Patients were screened for probing depth, bleeding on probing, clinical attachment level, and classified according to CDC/AAP criteria with or without periodontal dysbiosis. Serum inflammatory cytokines were measured by human cytokine panel and a targeted pathogenic subgingival biofilm panel was examined by DNA-DNA checkerboard from subgingival plaque samples. The results showed significant upregulation of serum proinflammatory cytokines in individuals with SLE when compared to controls. Stratification of subject's into SLE-inactive (I) and SLE-active (A) phenotypes or periodontitis and non-periodontitis groups provided new insights into SLE pathophysiology. Ten proinflammatory cytokines were upregulated in serum of SLE-I only and one in SLE-A only. Four molecules overlapped in SLE-A and SLE-I. Anti-inflammatory cytokines included IL-4 IL-10, which were upregulated in SLE-I sera (but not SLE-A), controlling clinical phenotypes. Out of 24 significant differential oral microbial abundances found in SLE, 14 unique subgingival bacteria profiles were found to be elevated in SLE. The most severe oral pathogens ( and ) showed increase abundances on SLE-A periodontal sites when compared to SLE-I and healthy controls. Inflammation as measured by cytokine-microbial correlations showed that periodontal pathogens dominating the environment increased proinflammatory cytokines systemically. Altogether, low-grade systemic inflammation that influenced SLE disease activity and severity was correlated to dysbiotic changes of the oral microbiota present in periodontal diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.02602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861327PMC
November 2020

Untargeted mass spectrometry-based metabolomics approach unveils molecular changes in raw and processed foods and beverages.

Food Chem 2020 Jan 30;302:125290. Epub 2019 Jul 30.

Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, United States; Center for Microbiome Innovation, University of California, San Diego, United States; Scripps Institution of Oceanography, University of California, San Diego, United States.

In our daily lives, we consume foods that have been transported, stored, prepared, cooked, or otherwise processed by ourselves or others. Food storage and preparation have drastic effects on the chemical composition of foods. Untargeted mass spectrometry analysis of food samples has the potential to increase our chemical understanding of these processes by detecting a broad spectrum of chemicals. We performed a time-based analysis of the chemical changes in foods during common preparations, such as fermentation, brewing, and ripening, using untargeted mass spectrometry and molecular networking. The data analysis workflow presented implements an approach to study changes in food chemistry that can reveal global alterations in chemical profiles, identify changes in abundance, as well as identify specific chemicals and their transformation products. The data generated in this study are publicly available, enabling the replication and re-analysis of these data in isolation, and serve as a baseline dataset for future investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2019.125290DOI Listing
January 2020

Identification of the Bacterial Biosynthetic Gene Clusters of the Oral Microbiome Illuminates the Unexplored Social Language of Bacteria during Health and Disease.

mBio 2019 04 16;10(2). Epub 2019 Apr 16.

Genomic Medicine Group, J. Craig Venter Institute, La Jolla, California, USA

Small molecules are the primary communication media of the microbial world. Recent bioinformatic studies, exploring the biosynthetic gene clusters (BGCs) which produce many small molecules, have highlighted the incredible biochemical potential of the signaling molecules encoded by the human microbiome. Thus far, most research efforts have focused on understanding the social language of the gut microbiome, leaving crucial signaling molecules produced by oral bacteria and their connection to health versus disease in need of investigation. In this study, a total of 4,915 BGCs were identified across 461 genomes representing a broad taxonomic diversity of oral bacteria. Sequence similarity networking provided a putative product class for more than 100 unclassified novel BGCs. The newly identified BGCs were cross-referenced against 254 metagenomes and metatranscriptomes derived from individuals either with good oral health or with dental caries or periodontitis. This analysis revealed 2,473 BGCs, which were differentially represented across the oral microbiomes associated with health versus disease. Coabundance network analysis identified numerous inverse correlations between BGCs and specific oral taxa. These correlations were present in healthy individuals but greatly reduced in individuals with dental caries, which may suggest a defect in colonization resistance. Finally, corroborating mass spectrometry identified several compounds with homology to products of the predicted BGC classes. Together, these findings greatly expand the number of known biosynthetic pathways present in the oral microbiome and provide an atlas for experimental characterization of these abundant, yet poorly understood, molecules and socio-chemical relationships, which impact the development of caries and periodontitis, two of the world's most common chronic diseases. The healthy oral microbiome is symbiotic with the human host, importantly providing colonization resistance against potential pathogens. Dental caries and periodontitis are two of the world's most common and costly chronic infectious diseases and are caused by a localized dysbiosis of the oral microbiome. Bacterially produced small molecules, often encoded by BGCs, are the primary communication media of bacterial communities and play a crucial, yet largely unknown, role in the transition from health to dysbiosis. This study provides a comprehensive mapping of the BGC repertoire of the human oral microbiome and identifies major differences in health compared to disease. Furthermore, BGC representation and expression is linked to the abundance of particular oral bacterial taxa in health versus dental caries and periodontitis. Overall, this study provides a significant insight into the chemical communication network of the healthy oral microbiome and how it devolves in the case of two prominent diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.00321-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469967PMC
April 2019

Microbe and plant assisted-remediation of organic xenobiotics and its enhancement by genetically modified organisms and recombinant technology: A review.

Sci Total Environ 2018 Jul 22;628-629:1582-1599. Epub 2018 Feb 22.

AIT Austrian Institute of Technology, Centre for Energy, Environmental Resources and Technologies, Tulln, Austria. Electronic address:

Environmental problems such as the deterioration of groundwater quality, soil degradation and various threats to human, animal and ecosystem health are closely related to the presence of high concentrations of organic xenobiotics in the environment. Employing appropriate technologies to remediate contaminated soils is crucial due to the site-specificity of most remediation methods. The limitations of conventional remediation technologies include poor environmental compatibility, high cost of implementation and poor public acceptability. This raises the call to employ biological methods for remediation. Bioremediation and microbe-assisted bioremediation (phytoremediation) offer many ecological and cost-associated benefits. The overall efficiency and performance of bio- and phytoremediation approaches can be enhanced by genetically modified microbes and plants. Moreover, phytoremediation can also be stimulated by suitable plant-microbe partnerships, i.e. plant-endophytic or plant-rhizospheric associations. Synergistic interactions between recombinant bacteria and genetically modified plants can further enhance the restoration of environments impacted by organic pollutants. Nevertheless, releasing genetically modified microbes and plants into the environment does pose potential risks. These can be minimized by adopting environmental biotechnological techniques and guidelines provided by environmental protection agencies and other regulatory frameworks. The current contribution provides a comprehensive overview on enhanced bioremediation and phytoremediation approaches using transgenic plants and microbes. It also sheds light on the mitigation of associated environmental risks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2018.02.037DOI Listing
July 2018

Secondary metabolite genes encoded by potato rhizosphere microbiomes in the Andean highlands are diverse and vary with sampling site and vegetation stage.

Sci Rep 2017 05 24;7(1):2330. Epub 2017 May 24.

AIT Austrian Institute of Technology GmbH, Center for Health & Bioresources, Bioresources Unit, Konrad Lorenz Straße 24, A-3430, Tulln, Austria.

Potato (Solanum tuberosum) is an important staple crop worldwide, it has been cultivated in the Andean Altiplano under low-input farming practices at high altitudes and under harsh environment for centuries. We analyzed secondary metabolite (SM) gene diversity encoded in the potato rhizosphere microbiome during plant growth at three distinct sites located in the Andes at high altitudes by 454-pyrosequencing of non-ribosomal peptide and polyketide biosynthetic genes. Phylogenetic analysis indicated that the majority of rhizosphere SM-encoding sequences differed from previously known sequences and may have distinct ancestors. In particular, actinobacterial methyl-malonyl-CoA transferase and acyl carrier protein from Firmicutes, both involved in the synthesis of SMs, showed widespread distribution of clades which were clearly distinct from sequences deposited in public databases, and only 11% of these sequences could be linked to the production of specific classes of SMs. Although the same cultivar was analyzed, SM gene composition radically differed among plant growth stages and across sites, suggesting a distinct repertoire of SM genes that likely encode diverse SM structures. Also, great diversity of non-ribosomal peptide and polyketide biosynthetic pathways in potato-associated microbiomes in the Andean highlands may represent a rich source of novel natural products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-02314-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443786PMC
May 2017

Surfactin variants mediate species-specific biofilm formation and root colonization in Bacillus.

Environ Microbiol 2016 09 4;18(8):2634-45. Epub 2016 Jul 4.

Health & Environment Department, Bioresources Unit, AIT Austrian Institute of Technology GmbH, AIT, Konrad Lorenz Strasse 24, Tulln, A-3430, Austria.

Cyclic lipopeptides (cLP) and especially surfactins produced by Bacillus spp. trigger biofilm formation and root colonization and are crucial for biocontrol activity and systemic resistance in plants. Bacillus atrophaeus 176s isolated from the moss Tortella tortuosa produces the cLP fengycins, iturins and surfactins, possesses antifungal activities and can protect tomato, lettuce and sugar beet against Rhizoctonia solani infection. In B. atrophaeus we identified for the first time the variant surfactin C, which differs from surfactin A produced by B. subtilis and B. amyloliquefaciens by an isoleucine instead of a leucine at position 7 of the lipopeptide backbone. The analysis of the complete surfactin gene clusters revealed that the dissimilarity is encoded in the adenylation domain of srfC and show that surfactin variations are distributed in a species-specific manner in bacilli. We demonstrate that the surfactin A and C with subtle structural differences have varying signal strengths on biofilm formation and root colonization and act specifically on the respective producing strain. This became evident as biofilm formation and root colonization but not swarming motility in surfactin biosynthesis mutants was restored differentially in the presence of exogenously supplemented cognate and non-cognate surfactin variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1462-2920.13405DOI Listing
September 2016

The Draft Genome Sequence of Paenibacillus polymyxa Strain CCI-25 Encompasses High Potential for Secondary Metabolite Production.

Genome Announc 2016 May 19;4(3). Epub 2016 May 19.

Bioresources Unit, Health and Environment Department, Austrian Institute of Technology (AIT), Tulln, Austria

We report here the draft genome sequence of Paenibacillus polymyxa strain CCI-25, which displays strong antifungal and antibacterial activities in vitro The genome encompasses nonribosomal peptide synthetases predicted to encode a tridecaptin, polymyxin, fusaricidin, an iturin-like synthetase, a lantibiotic similar to paenicidin A, as well as a type 1 polyketide synthase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/genomeA.00366-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889004PMC
May 2016

Genome mining: Prediction of lipopeptides and polyketides from Bacillus and related Firmicutes.

Comput Struct Biotechnol J 2015 24;13:192-203. Epub 2015 Mar 24.

AIT Austrian Institute of Technology GmbH, AIT, Health & Environment Department, Bioresources Unit, Konrad Lorenz Strasse 24, A-3430 Tulln, Austria.

Bacillus and related genera in the Bacillales within the Firmicutes harbor a variety of secondary metabolite gene clusters encoding polyketide synthases and non-ribosomal peptide synthetases responsible for remarkable diverse number of polyketides (PKs) and lipopeptides (LPs). These compounds may be utilized for medical and agricultural applications. Here, we summarize the knowledge on structural diversity and underlying gene clusters of LPs and PKs in the Bacillales. Moreover, we evaluate by using published prediction tools the potential metabolic capacity of these bacteria to produce type I PKs or LPs. The huge sequence repository of bacterial genomes and metagenomes provides the basis for such genome-mining to reveal the potential for novel structurally diverse secondary metabolites. The otherwise cumbersome task to isolate often unstable PKs and deduce their structure can be streamlined. Using web based prediction tools, we identified here several novel clusters of PKs and LPs from genomes deposited in the database. Our analysis suggests that a substantial fraction of predicted LPs and type I PKs are uncharacterized, and their functions remain to be studied. Known and predicted LPs and PKs occurred in the majority of the plant associated genera, predominantly in Bacillus and Paenibacillus. Surprisingly, many genera from other environments contain no or few of such compounds indicating the role of these secondary metabolites in plant-associated niches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.csbj.2015.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397504PMC
April 2015

Wake-up-call, a lin-52 paralogue, and Always early, a lin-9 homologue physically interact, but have opposing functions in regulating testis-specific gene expression.

Dev Biol 2011 Jul 4;355(2):381-93. Epub 2011 May 4.

Department of Zoology, University of Oxford, South Parks Rd, Oxford, OX1 3PS, UK.

A conserved multi-subunit complex (MybMuvB, MMB), regulates transcriptional activity of many different target genes in Drosophila somatic cells. A paralogous complex, tMAC, controls expression of at least 1500 genes in the male germline, and is essential for sperm production. The roles of specific subunits of tMAC, MMB or orthologous complexes in regulating target gene expression are not understood. MMB and orthologous complexes have Lin-52 as a subunit, but Lin-52 did not co-purify with tMAC. We identified wake-up-call (wuc), a lin-52 paralogue, via a physical interaction with the tMAC lin-9-related subunit Aly, and find that Wuc co-localises with known tMAC subunits. We show that wuc, like aly, is required for spermatogenesis. However, despite phenotypic similarities, the role of wuc is very different from that of previously characterised tMAC mutants. Unlike aly, loss of wuc results in only relatively mild defects in testis-specific gene expression. Strikingly, wuc loss of function partially rescues expression of target genes in aly mutant testes. We propose that wuc represses testis-specific gene expression, that this repression is counteracted by aly, and that aly and a testis-specific TF(II)D complex work together to promote high transcriptional activity of spermiogenic genes specifically in primary spermatocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ydbio.2011.04.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123737PMC
July 2011
-->