Manesh Shah

Manesh Shah
University of Tennessee | UTK · Department of Genome Science and Technology

About

219
Publications
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Introduction
Protein structure prediction, molecular modeling

Publications

Publications (219)
Preprint
We developed Distilled Graph Attention Policy Networks (DGAPNs), a curiosity-driven reinforcement learning model to generate novel graph-structured chemical representations that optimize user-defined objectives by efficiently navigating a physically constrained domain. The framework is examined on the task of generating molecules that are designed...
Article
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Background A mechanistic understanding of the spread of SARS-CoV-2 and diligent tracking of ongoing mutagenesis are of key importance to plan robust strategies for confining its transmission. Large numbers of available sequences and their dates of transmission provide an unprecedented opportunity to analyze evolutionary adaptation in novel ways. Ad...
Article
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Government retains a non-exclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan...
Article
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Despite SARS-CoV and SARS-CoV-2 being equipped with highly similar protein arsenals, the corresponding zoonoses have spread among humans at extremely different rates. The specific characteristics of these viruses that led to such distinct outcomes remain unclear. Here, we apply proteome-wide comparative structural analysis aiming to identify the un...
Chapter
We demonstrate a selection of network and machine learning techniques useful in the analysis of complex datasets, including 2-way similarity networks, Markov clustering, enrichment statistical networks, FCROS differential analysis, and random forests. We demonstrate each of these techniques on the Populus trichocarpa gene expression atlas.
Preprint
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Using a Systems Biology approach, we integrated genomic, transcriptomic, proteomic, and molecular structure information to provide a holistic understanding of the COVID-19 pandemic. The expression data analysis of the Renin Angiotensin System indicates mild nasal, oral or throat infections are likely and that the gastrointestinal tissues are a comm...
Article
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Various 'omics data types have been generated for Populus trichocarpa, each providing a layer of information which can be represented as a density signal across a chromosome. We make use of genome sequence data, variants data across a population as well as methylation data across 10 different tissues, combined with wavelet-based signal processing t...
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Various patterns of multi-phenotype associations (MPAs) exist in the results of Genome Wide Association Studies (GWAS) involving different topologies of single nucleotide polymorphism (SNP)-phenotype associations. These can provide interesting information about the different impacts of a gene on closely related phenotypes or disparate phenotypes (p...
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Biological organisms are complex systems that are composed of functional networks of interacting molecules and macro-molecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current env...
Preprint
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Biological organisms are complex systems that are composed of functional networks of interacting molecules and macromolecules. Complex phenotypes are the result of orchestrated, hierarchical, heterogeneous collections of expressed genomic variants. However, the effects of these variants are the result of historic selective pressure and current envi...
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Background: Metabolic engineering is a commonly used approach to develop organisms for an industrial function, but engineering aimed at improving one phenotype can negatively impact other phenotypes. This lack of robustness can prove problematic. Cellulolytic bacterium Clostridium thermocellum is able to rapidly ferment cellulose to ethanol and ot...
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Over 20% of Earth's terrestrial surface is underlain by permafrost with vast stores of carbon that, once thawed, may represent the largest future transfer of carbon from the biosphere to the atmosphere. This process is largely dependent on microbial responses, but we know little about microbial activity in intact, let alone in thawing, permafrost....
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GPI-anchored proteins (GPI-APs) are an important class of glycoproteins that are tethered to the surface of mammalian cells via the lipid glycosylphosphatidylinositol (GPI). GPI-APs have been implicated in many important cellular functions including cell adhesion, cell signaling, and immune regulation. Proteomic identification of mammalian GPI-APs...
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The squid, Euprymna scolopes, and the luminescent bacterium, Vibrio fischeri, form a highly specific beneficial light organ symbiosis. Not only does the host have to select V. fischeri from the environment, but it must also prevent subsequent colonization by non-symbiotic microorganisms. Host macrophage-like hemocytes are believed to play a role in...
Article
High performance mass spectrometry instrumentation coupled with improved protein extraction techniques enables metaproteomics to identify active members of soil and groundwater microbial communities. Metaproteomics workflows were applied to study the initial responses (i.e., 4 days post treatment) of the indigenous aquifer microbiota to biostimulat...
Article
Viruses are fundamental to ecosystems ranging from oceans to humans, yet our ability to study them is bottlenecked by the lack of ecologically relevant isolates, resulting in "unknowns" dominating culture-independent surveys. Here we present genomes from 31 phages infecting multiple strains of the aquatic bacterium Cellulophaga baltica (Bacteroidet...
Data
Organism normalized spectral abundance factor (NSAF) values (relative abundance) for the γ1 symbiont transposases. Minimum number of γ1 symbiont transposase proteins needed to explain all detected peptides (according to the grouping in Table S4 in the supplemental material). The values in the table are NSAF, which indicate the relative abundance of...
Data
NSAF values (relative abundance) of expressed transposases.
Data
Organism NSAF values for the δ1 symbiont transposases. Minimum number of δ1 symbiont transposase proteins needed to explain all detected peptides (according to the grouping in Table S4 in the supplemental material). The values in the table are NSAF, which indicate the relative abundance of the respective protein in relation to all identified δ1 sym...
Data
Identified transposases grouped according to the peptides with which they were detected.
Article
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Leptospirillum spp. are widespread members of acidophilic microbial communities that catalyze ferrous iron oxidation, thereby increasing sulfide mineral dissolution rates. These bacteria play important roles in environmental acidification and are harnessed for bioleaching-based metal recovery. Known members of the Leptospirillum clade of the Nitros...
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Microbial ferrous iron [Fe(II)] oxidation leads to the formation of iron-rich macroscopic aggregates (“iron snow”) at the redoxcline in a stratified lignite mine lake in east-central Germany. We aimed to identify the abundant Fe-oxidizing and Fe-reducing microorganisms likely to be involved in the formation and transformation of iron snow present i...
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IMPORTANCE The expansion of transposable elements (TE) within the genomes of host-restricted symbionts and pathogens plays an important role in their emergence and evolution and might be a key mechanism for adaptation to the host environment. However, little is known so far about the underlying causes and evolutionary mechanisms of this TE expansio...
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Archaea are widely distributed and yet are most often not the most abundant members of microbial communities. Here, we document a transition from Bacteria- to Archaea-dominated communities in microbial biofilms sampled from the Richmond Mine acid mine drainage (AMD) system (∼pH 1.0, ∼38°C) and in laboratory-cultivated biofilms. This transition occu...
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Stimulation of subsurface microorganisms to induce reductive immobilization of metals is a promising approach for bioremediation, yet the overall microbial community response is typically poorly understood. Here we used proteogenomics to test the hypothesis that excess input of acetate activates complex community functioning and syntrophic interact...
Article
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Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs t...
Data
Human microbial isolate reference genome database (HMRG) database components. 51 bacterial isolates were downloaded from the JGI IMG human microbiome project (IMG-HMP) into a single FASTA-formatted protein sequence database. (XLSX)
Data
Full-text available
Additional figures, tables, a note regarding technical and twin reproducibility in the metaproteomes and peptide-level false discovery rates. (PDF)
Data
Distribution of all normalized ‘unique’ spectra counts (worksheet 1) for a metaproteome genus-level comparison of all 24 MS runs against the HMRG database. Three comparisons (worksheet 2–4) between different phenotypes (healthy, ICD, and CCD) were performed with Wilson rank sum: Q value (adjusted P value) less than 0.05, difference between medians...
Data
Core and unique microbial protein clusters identified in the metaproteomes. Common core microbial protein clusters (worksheet 1) identified in the metaproteomes of all subjects included in the study (healthy, ICD and CCD). Microbial protein clusters that were identified as unique to one phenotype, healthy (worksheet 2), ICD (worksheet 3), and CCD (...
Article
The expanding use of surfactants for proteome sample preparations has prompted the need to systematically optimize the application and removal of these MS-deleterious agents prior to proteome measurements. Here we compare four different detergent clean-up methods (Trichloroacetic acid (TCA) precipitation, Chloroform/Methanol/Water (CMW) extraction,...
Conference Paper
The fate of organic carbon reserves sequestered in permafrost is uncertain yet critically important for addressing terrestrial feedbacks to climate change. With warming there is an increased probability of thermokarst formation, and an increase in CO2 and CH4 flux to the atmosphere. However, we understand little of the underlying microbial controls...
Article
System biology and bioprocess technology can be better understood using shotgun proteomics as a monitoring system during the fermentation. We demonstrated a shotgun proteomic method to monitor the temporal yeast proteome in early, middle and late exponential phases. Our study identified a total of 1389 proteins combining all 2D-LC-MS/MS runs. The t...
Article
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The CRISPR/Cas system, comprised of clustered regularly interspaced short palindromic repeats along with their associated (Cas) proteins, protects bacteria and archaea from viral predation and invading nucleic acids. While the mechanism of action for this acquired immunity is currently under investigation, the response of Cas protein expression to...
Data
Proteomic Analysis of a Bacteriophage Insensitive Mutant (BIM). S. thermophilus DGCC7710 was infected at an MOI = 0.1 with phage 2972, and mounted a CRISPR response becoming phage resistant. This bacteriophage insensitive mutant, BIM, was co-cultured with the phage for fifty generations, after which the proteome was measured using nano-2D-LC-MS/MS....
Data
Full-text available
Reproducibility between technical replicates. Normalized spectral counts from two technical replicates plotted against each other, with replicate 1 on the y-axis and replicate 2 on the x-axis. A linear regression was performed, and the slope of the line (m), and R2 values calculated providing a statistical measure (a value between zero to one) indi...
Data
Proteins changing at each time point in relation to time 0 at MOIs = 1, 0.1, and 0. (XLSX)
Data
Proteins changing from T0 to early infection, early infection to peak infection, and T0 to peak infection at MOI = 1 and MOI = 0.1. (XLSX)
Data
Full-text available
Color-coded representation of protein abundance changes for all detected proteins across the time courses. The Poisson exact test was used to determine proteins which were significantly increased or decreased in abundance with respect to time 0. Each line represents a single protein and is colored red if increased, green if decreased, and black if...
Data
All proteins detected throughout infection time course. (XLSX)
Article
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Low nutrient and energy availability has led to the evolution of numerous strategies for overcoming these limitations, of which symbiotic associations represent a key mechanism. Particularly striking are the associations between chemosynthetic bacteria and marine animals that thrive in nutrient-poor environments such as the deep sea because the sym...
Article
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Economically viable production of solvents through acetone-butanol-ethanol (ABE) fermentation requires a detailed understanding of Clostridium acetobutylicum. This study focuses on the proteomic profiling of C. acetobutylicum ATCC 824 from the stationary phase of ABE fermentation using xylose and compares with the exponential growth by shotgun prot...
Conference Paper
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Acidobacteria were dominant and ubiquitous in all sites, consistent with members of this phylum being adapted to low energy, low nutrient, highly acidic and water stressed environments. Changes in microbial community structure along the thaw gradient were substantial, with the largest difference occurring at the oxic/anoxic boundary. Microbial comm...
Article
Current state-of-the-art experimental and computational proteomic approaches were integrated to obtain a comprehensive protein profile of Populus vascular tissue. This featured: (1) a large sample set consisting of two genotypes grown under normal and tension stress conditions, (2) bioinformatics clustering to effectively handle gene duplication, a...
Article
Full-text available
Bacteria of the genus Dehalococcoides play an important role in the reductive dechlorination of chlorinated ethenes. A systems-level approach was taken in this study to examine the global transcriptomic and proteomic responses of exponentially growing cells of Dehalococcoides ethenogenes strain 195 to fixed nitrogen limitation (FNL), as dechlorinat...
Data
Accuracy Assessment by DTASelect Filtering. (a) For each DTASelect peptide prediction search, the number of identified spectra was calculated and compared using three different parameter combinations, deltCN filtered results at a deltCN of 0.08 only, both deltCN of 0.08 and HM (±10 ppm), and HM (±10 ppm) only, where identified peptide sequences wer...
Data
False discovery rates for sample 6b (Run 1 and 2) against the RMPS database. An initial ≥1-peptide, deltCN 0.0, and high mass accuracy (±10 ppm) filter were applied to the read-based identifications followed by a ≥2-peptide/protein post-database mapping filter. (XLS)
Data
Additional supporting information and results for the protein sequence database comparisons, tracking missing peptides, and de novo peptide sequencing. (DOC)
Data