Biogeochemical models for predicting carbon dynamics increasingly include microbial processes, reflecting the importance of microorganisms in regulating the movement of carbon between soils and the atmosphere. Soil viruses can redirect carbon among various chemical pools, indicating a need for quantification and development soil carbon models that explicitly represent viral dynamics. In this opinion, we derive a global estimate of carbon potentially released from microbial biomass by viral infections in soils and synthesize a quantitative soil carbon budget from existing literature that explicitly includes viral impacts.
View Article and Find Full Text PDFUbiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence or structural homology to eukaryotic ubiquitin regulators.
View Article and Find Full Text PDFHistorically neglected by microbial ecologists, soil viruses are now thought to be critical to global biogeochemical cycles. However, our understanding of their global distribution, activities and interactions with the soil microbiome remains limited. Here we present the Global Soil Virus Atlas, a comprehensive dataset compiled from 2,953 previously sequenced soil metagenomes and composed of 616,935 uncultivated viral genomes and 38,508 unique viral operational taxonomic units.
View Article and Find Full Text PDFThe reconstruction of complete microbial metabolic pathways using 'omics data from environmental samples remains challenging. Computational pipelines for pathway reconstruction that utilize machine learning methods to predict the presence or absence of KEGG modules in incomplete genomes are lacking. Here, we present MetaPathPredict, a software tool that incorporates machine learning models to predict the presence of complete KEGG modules within bacterial genomic datasets.
View Article and Find Full Text PDFCircadian misalignment due to night work has been associated with an elevated risk for chronic diseases. We investigated the effects of circadian misalignment using shotgun protein profiling of peripheral blood mononuclear cells taken from healthy humans during a constant routine protocol, which was conducted immediately after participants had been subjected to a 3-day simulated night shift schedule or a 3-day simulated day shift schedule. By comparing proteomic profiles between the simulated shift conditions, we identified proteins and pathways that are associated with the effects of circadian misalignment and observed that insulin regulation pathways and inflammation-related proteins displayed markedly different temporal patterns after simulated night shift.
View Article and Find Full Text PDFHigh-density lipoproteins (HDLs) are promising targets for predicting and treating atherosclerotic cardiovascular disease (ASCVD), as they mediate removal of excess cholesterol from lipid-laden macrophages that accumulate in the vasculature. This functional property of HDLs, termed cholesterol efflux capacity (CEC), is inversely associated with ASCVD. HDLs are compositionally diverse, associating with >250 different proteins, but their relative contribution to CEC remains poorly understood.
View Article and Find Full Text PDFAnnu Rev Pharmacol Toxicol
January 2024
Proteogenomics refers to the integration of comprehensive genomic, transcriptomic, and proteomic measurements from the same samples with the goal of fully understanding the regulatory processes converting genotypes to phenotypes, often with an emphasis on gaining a deeper understanding of disease processes. Although specific genetic mutations have long been known to drive the development of multiple cancers, gene mutations alone do not always predict prognosis or response to targeted therapy. The benefit of proteogenomics research is that information obtained from proteins and their corresponding pathways provides insight into therapeutic targets that can complement genomic information by providing an additional dimension regarding the underlying mechanisms and pathophysiology of tumors.
View Article and Find Full Text PDFLipoproteins in cerebrospinal fluid (CSF) of the central nervous system (CNS) resemble plasma high-density lipoproteins (HDLs), which are a compositionally and structurally diverse spectrum of nanoparticles with pleiotropic functionality. Whether CSF lipoproteins (CSF-Lps) exhibit similar heterogeneity is poorly understood because they are present at 100-fold lower concentrations than plasma HDL. To investigate the diversity of CSF-Lps, we developed a sensitive fluorescent technology to characterize lipoprotein subspecies in small volumes of human CSF.
View Article and Find Full Text PDFBackground: Microbiomes contribute to multiple ecosystem services by transforming organic matter in the soil. Extreme shifts in the environment, such as drying-rewetting cycles during drought, can impact the microbial metabolism of organic matter by altering microbial physiology and function. These physiological responses are mediated in part by lipids that are responsible for regulating interactions between cells and the environment.
View Article and Find Full Text PDFMotivation: The vast expansion of sequence data generated from single organisms and microbiomes has precipitated the need for faster and more sensitive methods to assess evolutionary and functional relationships between proteins. Representing proteins as sets of short peptide sequences (kmers) has been used for rapid, accurate classification of proteins into functional categories; however, this approach employs an exact-match methodology and thus may be limited in terms of sensitivity and coverage. We have previously used similarity groupings, based on the chemical properties of amino acids, to form reduced character sets and recode proteins.
View Article and Find Full Text PDFis likely the most common bacterial cause of gastroenteritis worldwide, responsible for millions of cases of inflammatory diarrhea characterized by severe abdominal cramps and blood in the stool. Further, infections are associated with post-infection sequelae in developed countries and malnutrition and growth-stunting in low- and middle-income countries. Despite the increasing prevalence of the disease, campylobacteriosis, and the recognition that this pathogen is a serious health threat, our understanding of pathogenesis remains incomplete.
View Article and Find Full Text PDFMetagenomics is unearthing the previously hidden world of soil viruses. Many soil viral sequences in metagenomes contain putative auxiliary metabolic genes (AMGs) that are not associated with viral replication. Here, we establish that AMGs on soil viruses actually produce functional, active proteins.
View Article and Find Full Text PDFAcute Myeloid Leukemia (AML) affects 20,000 patients in the US annually with a five-year survival rate of approximately 25%. One reason for the low survival rate is the high prevalence of clonal evolution that gives rise to heterogeneous sub-populations of leukemic cells with diverse mutation spectra, which eventually leads to disease relapse. This genetic heterogeneity drives the activation of complex signaling pathways that is reflected at the protein level.
View Article and Find Full Text PDFSoil viruses are abundant, but the influence of the environment and climate on soil viruses remains poorly understood. Here, we addressed this gap by comparing the diversity, abundance, lifestyle, and metabolic potential of DNA viruses in three grassland soils with historical differences in average annual precipitation, low in eastern Washington (WA), high in Iowa (IA), and intermediate in Kansas (KS). Bioinformatics analyses were applied to identify a total of 2,631 viral contigs, including 14 complete viral genomes from three deep metagenomes (1 terabase [Tb] each) that were sequenced from bulk soil DNA.
View Article and Find Full Text PDFCardiac endothelial cells respond to both ischemia and therapeutic ultrasound; the proteomic changes underlying these responses are unknown. This data article provides raw and processed data resulting from our global, unbiased phosphoproteomics investigation conducted on primary mouse cardiac endothelial cells exposed to ischemia (2-hour oxygen glucose deprivation) and ultrasound (250 kHz, 1.2 MPa) in vitro [1].
View Article and Find Full Text PDFSoil is known to harbor viruses, but the majority are uncharacterized and their responses to environmental changes are unknown. Here, we used a multi-omics approach (metagenomics, metatranscriptomics and metaproteomics) to detect active DNA viruses and RNA viruses in a native prairie soil and to determine their responses to extremes in soil moisture. The majority of transcribed DNA viruses were bacteriophage, but some were assigned to eukaryotic hosts, mainly insects.
View Article and Find Full Text PDFOur study details the stepwise evolution of gilteritinib resistance in FLT3-mutated acute myeloid leukemia (AML). Early resistance is mediated by the bone marrow microenvironment, which protects residual leukemia cells. Over time, leukemia cells evolve intrinsic mechanisms of resistance, or late resistance.
View Article and Find Full Text PDFBiochim Biophys Acta Proteins Proteom
September 2021
Myocardial infarction and subsequent therapeutic interventions activate numerous intracellular cascades in every constituent cell type of the heart. Endothelial cells produce several protective compounds in response to therapeutic ultrasound, under both normoxic and ischemic conditions. How endothelial cells sense ultrasound and convert it to a beneficial biological response is not known.
View Article and Find Full Text PDFMultiple arogenate dehydratase () knock-out (KO) mutants, with phenotypes having variable lignin levels (up to 70% reduction), were studied to investigate how differential reductions in ADTs perturb its overall plant systems biology. Integrated "omics" analyses (metabolome, transcriptome, and proteome) of wild type (WT), single and multiple KO lines were conducted. Transcriptome and proteome data were collapsed into gene ortholog (GO) data, with this allowing for enzymatic reaction and metabolome cross-comparisons to uncover dominant or likely metabolic biosynthesis reactions affected.
View Article and Find Full Text PDFBackground: Representing biological networks as graphs is a powerful approach to reveal underlying patterns, signatures, and critical components from high-throughput biomolecular data. However, graphs do not natively capture the multi-way relationships present among genes and proteins in biological systems. Hypergraphs are generalizations of graphs that naturally model multi-way relationships and have shown promise in modeling systems such as protein complexes and metabolic reactions.
View Article and Find Full Text PDF