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1.
BMC Bioinformatics ; 23(Suppl 1): 29, 2022 Jan 10.
Article in English | MEDLINE | ID: mdl-35012449

ABSTRACT

BACKGROUND: DNA methylation has long been known as an epigenetic gene silencing mechanism. For a motivating example, the methylomes of cancer and non-cancer cells show a number of methylation differences, indicating that certain features characteristics of cancer cells may be related to methylation characteristics. Robust methods for detecting differentially methylated regions (DMRs) could help scientists narrow down genome regions and even find biologically important regions. Although some statistical methods were developed for detecting DMR, there is no default or strongest method. Fisher's exact test is direct, but not suitable for data with multiple replications, while regression-based methods usually come with a large number of assumptions. More complicated methods have been proposed, but those methods are often difficult to interpret. RESULTS: In this paper, we propose a three-step nonparametric kernel smoothing method that is both flexible and straightforward to implement and interpret. The proposed method relies on local quadratic fitting to find the set of equilibrium points (points at which the first derivative is 0) and the corresponding set of confidence windows. Potential regions are further refined using biological criteria, and finally selected based on a Bonferroni adjusted t-test cutoff. Using a comparison of three senescent and three proliferating cell lines to illustrate our method, we were able to identify a total of 1077 DMRs on chromosome 21. CONCLUSIONS: We proposed a completely nonparametric, statistically straightforward, and interpretable method for detecting differentially methylated regions. Compared with existing methods, the non-reliance on model assumptions and the straightforward nature of our method makes it one competitive alternative to the existing statistical methods for defining DMRs.


Subject(s)
DNA Methylation , Genome , CpG Islands , Entropy , Epigenesis, Genetic
2.
BMC Genomics ; 23(1): 45, 2022 Jan 11.
Article in English | MEDLINE | ID: mdl-35012450

ABSTRACT

BACKGROUND: Orius laevigatus, a minute pirate bug, is a highly effective beneficial predator of crop pests including aphids, spider mites and thrips in integrated pest management (IPM) programmes. No genomic information is currently available for O. laevigatus, as is the case for the majority of beneficial predators which feed on crop pests. In contrast, genomic information for crop pests is far more readily available. The lack of publicly available genomes for beneficial predators to date has limited our ability to perform comparative analyses of genes encoding potential insecticide resistance mechanisms between crop pests and their predators. These mechanisms include several gene/protein families including cytochrome P450s (P450s), ATP binding cassette transporters (ABCs), glutathione S-transferases (GSTs), UDP-glucosyltransferases (UGTs) and carboxyl/cholinesterases (CCEs). METHODS AND FINDINGS: In this study, a high-quality scaffold level de novo genome assembly for O. laevigatus has been generated using a hybrid approach with PacBio long-read and Illumina short-read data. The final assembly achieved a scaffold N50 of 125,649 bp and a total genome size of 150.98 Mb. The genome assembly achieved a level of completeness of 93.6% using a set of 1658 core insect genes present as full-length genes. Genome annotation identified 15,102 protein-coding genes - 87% of which were assigned a putative function. Comparative analyses revealed gene expansions of sigma class GSTs and CYP3 P450s. Conversely the UGT gene family showed limited expansion. Differences were seen in the distributions of resistance-associated gene families at the subfamily level between O. laevigatus and some of its targeted crop pests. A target site mutation in ryanodine receptors (I4790M, PxRyR) which has strong links to diamide resistance in crop pests and had previously only been identified in lepidopteran species was found to also be present in hemipteran species, including O. laevigatus. CONCLUSION AND SIGNIFICANCE: This assembly is the first published genome for the Anthocoridae family and will serve as a useful resource for further research into target-site selectivity issues and potential resistance mechanisms in beneficial predators. Furthermore, the expansion of gene families often linked to insecticide resistance may be an indicator of the capacity of this predator to detoxify selective insecticides. These findings could be exploited by targeted pesticide screens and functional studies to increase effectiveness of IPM strategies, which aim to increase crop yields by sustainably, environmentally-friendly and effectively control pests without impacting beneficial predator populations.


Subject(s)
Heteroptera , Insecticides , Thysanoptera , Animals , Genome , Humans , Insecticide Resistance
3.
BMC Res Notes ; 15(1): 8, 2022 Jan 10.
Article in English | MEDLINE | ID: mdl-35012607

ABSTRACT

OBJECTIVE: In addition to its function as the microtubule organizing center of the cell, the centrosome has functions in many other cellular processes including primary cilia formation, DNA damage checkpoints, and cell cycle progression. But the role of individual components of the centrosome in these processes remains unclear. Previous studies used siRNA (small interfering RNA) to "knock down" protein levels of the centrosome component centriolin, resulting in failed cytokinesis. Since this approach was transient, only targeting centriolin at the mRNA level, we sought to confirm these findings by permanently disrupting the gene encoding centriolin using the CRISPR/Cas9 system of genome editing. RESULTS: This study provides evidence that the CRISPR/Cas9 system is capable of effectively reducing centriolin protein levels in the cell. Furthermore, this disruption leads to a failure of cytokinesis that is reminiscent of the phenotype previously reported for the siRNA-mediated disruption of centriolin. Furthermore, no additional defects in cell division were observed, consistent with results seen with previous siRNA studies. We conclude that the CRISPR/Cas9 system is an effective means of permanently removing the cellular pools of centriolin and that the disruption of centriolin at both the mRNA level and genomic level lead to similar cell division defects.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Cytokinesis , Genome , RNA, Small Interfering
4.
BMC Bioinformatics ; 23(1): 33, 2022 Jan 11.
Article in English | MEDLINE | ID: mdl-35016614

ABSTRACT

BACKGROUND: The recent advancements in high-throughput sequencing have resulted in the availability of annotated genomes, as well as of multi-omics data for many living organisms. This has increased the need for graphic tools that allow the concurrent visualization of genomes and feature-associated multi-omics data on single publication-ready plots. RESULTS: We present chromoMap, an R package, developed for the construction of interactive visualizations of chromosomes/chromosomal regions, mapping of any chromosomal feature with known coordinates (i.e., protein coding genes, transposable elements, non-coding RNAs, microsatellites, etc.), and chromosomal regional characteristics (i.e. genomic feature density, gene expression, DNA methylation, chromatin modifications, etc.) of organisms with a genome assembly. ChromoMap can also integrate multi-omics data (genomics, transcriptomics and epigenomics) in relation to their occurrence across chromosomes. ChromoMap takes tab-delimited files (BED like) or alternatively R objects to specify the genomic co-ordinates of the chromosomes and elements to annotate. Rendered chromosomes are composed of continuous windows of a given range, which, on hover, display detailed information about the elements annotated within that range. By adjusting parameters of a single function, users can generate a variety of plots that can either be saved as static image or as HTML documents. CONCLUSIONS: ChromoMap's flexibility allows for concurrent visualization of genomic data in each strand of a given chromosome, or of more than one homologous chromosome; allowing the comparison of multi-omic data between genotypes (e.g. species, varieties, etc.) or between homologous chromosomes of phased diploid/polyploid genomes. chromoMap is an extensive tool that can be potentially used in various bioinformatics analysis pipelines for genomic visualization of multi-omics data.


Subject(s)
Genomics , Software , Chromosomes/genetics , Computational Biology , Genome
5.
Cell Mol Life Sci ; 79(1): 22, 2022 Jan 03.
Article in English | MEDLINE | ID: mdl-34981210

ABSTRACT

The three-dimensional configuration of the genome ensures cell type-specific gene expression profiles by placing genes and regulatory elements in close spatial proximity. Here, we used in situ high-throughput chromosome conformation (in situ Hi-C), RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to characterize the high-order chromatin structure signature of female germline stem cells (FGSCs) and identify its regulating key factor based on the data-driven of multiple omics data. By comparison with pluripotent stem cells (PSCs), adult stem cells (ASCs), and somatic cells at three major levels of chromatin architecture, A/B compartments, topologically associating domains, and chromatin loops, the chromatin architecture of FGSCs was most similar to that of other ASCs and largely different from that of PSCs and somatic cells. After integrative analysis of the three-dimensional chromatin structure, active compartment-associating loops (aCALs) were identified as a signature of high-order chromatin organization in FGSCs, which revealed that CCCTC-binding factor was a major factor to maintain the properties of FGSCs through regulation of aCALs. We found FGSCs belong to ASCs at chromatin structure level and characterized aCALs as the high-order chromatin structure signature of FGSCs. Furthermore, CTCF was identified to play a key role in regulating aCALS to maintain the biological functions of FGSCs. These data provide a valuable resource for future studies of the features of chromatin organization in mammalian stem cells and further understanding of the fundamental characteristics of FGSCs.


Subject(s)
CCCTC-Binding Factor/metabolism , Genome , Imaging, Three-Dimensional , Oogonial Stem Cells/metabolism , Adult Stem Cells/metabolism , Animals , Base Sequence , Cell Shape , Chromatin/metabolism , Chromosomes, Mammalian/metabolism , Female , Induced Pluripotent Stem Cells/metabolism , Male , Mice, Inbred C57BL , Oogonial Stem Cells/cytology
6.
BMC Bioinformatics ; 23(1): 37, 2022 Jan 12.
Article in English | MEDLINE | ID: mdl-35021991

ABSTRACT

BACKGROUND: LINCS, "Library of Integrated Network-based Cellular Signatures", and IDG, "Illuminating the Druggable Genome", are both NIH projects and consortia that have generated rich datasets for the study of the molecular basis of human health and disease. LINCS L1000 expression signatures provide unbiased systems/omics experimental evidence. IDG provides compiled and curated knowledge for illumination and prioritization of novel drug target hypotheses. Together, these resources can support a powerful new approach to identifying novel drug targets for complex diseases, such as Parkinson's disease (PD), which continues to inflict severe harm on human health, and resist traditional research approaches. RESULTS: Integrating LINCS and IDG, we built the Knowledge Graph Analytics Platform (KGAP) to support an important use case: identification and prioritization of drug target hypotheses for associated diseases. The KGAP approach includes strong semantics interpretable by domain scientists and a robust, high performance implementation of a graph database and related analytical methods. Illustrating the value of our approach, we investigated results from queries relevant to PD. Approved PD drug indications from IDG's resource DrugCentral were used as starting points for evidence paths exploring chemogenomic space via LINCS expression signatures for associated genes, evaluated as target hypotheses by integration with IDG. The KG-analytic scoring function was validated against a gold standard dataset of genes associated with PD as elucidated, published mechanism-of-action drug targets, also from DrugCentral. IDG's resource TIN-X was used to rank and filter KGAP results for novel PD targets, and one, SYNGR3 (Synaptogyrin-3), was manually investigated further as a case study and plausible new drug target for PD. CONCLUSIONS: The synergy of LINCS and IDG, via KG methods, empowers graph analytics methods for the investigation of the molecular basis of complex diseases, and specifically for identification and prioritization of novel drug targets. The KGAP approach enables downstream applications via integration with resources similarly aligned with modern KG methodology. The generality of the approach indicates that KGAP is applicable to many disease areas, in addition to PD, the focus of this paper.


Subject(s)
Parkinson Disease , Gene Library , Genome , Humans , Lighting , Parkinson Disease/drug therapy , Parkinson Disease/genetics , Pattern Recognition, Automated
7.
Methods Mol Biol ; 2404: 281-298, 2022.
Article in English | MEDLINE | ID: mdl-34694615

ABSTRACT

Polyadenylation and deadenylation of mRNA are major RNA modifications associated with nucleus-to-cytoplasm translocation, mRNA stability, translation efficiency, and mRNA decay pathways. Our current knowledge of polyadenylation and deadenylation has been expanded due to recent advances in transcriptome-wide poly(A) tail length assays. Whereas these methods measure poly(A) length by quantifying the adenine (A) base stretch at the 3' end of mRNA, we developed a more cost-efficient technique that does not rely on A-base counting, called tail-end-displacement sequencing (TED-seq). Through sequencing highly size-selected 3' RNA fragments including the poly(A) tail pieces, TED-seq provides accurate measure of transcriptome-wide poly(A)-tail lengths in high resolution, economically suitable for larger scale analysis under various biologically transitional contexts.


Subject(s)
Polyadenylation , Genome , Poly A/genetics , Poly A/metabolism , RNA Stability , RNA, Messenger/genetics , RNA, Messenger/metabolism , Sequence Analysis, RNA
8.
Methods Mol Biol ; 2396: 35-46, 2022.
Article in English | MEDLINE | ID: mdl-34786674

ABSTRACT

The similarity of biological functions and molecular mechanisms in living organisms suggests their common origin. The inference of evolutionary relationships among the extant organisms is primarily based on structural, functional, and sequence data of biomolecules, such as DNA, RNA, and protein, and their relative changes over the course of time. To decipher evolutionary relationships, a variety of data can be used. The exponential growth of genomic data, spurred by advances in DNA sequencing, has enabled biologists to reconstruct the tree or network of life for a vast number of organisms dwelling in the earth. In addition of organismal relationships, phylogenetic analysis is often performed to characterize gene families, specifically to identify the orthologs and paralogs of a gene of interest and understand their varied functions in light of evolution. In this chapter, we describe a protocol for reconstructing a phylogenetic tree using maximum-likelihood approach. We demonstrate using an example dataset and a suite of publicly available programs.


Subject(s)
Phylogeny , Evolution, Molecular , Genome , Genomics , Humans , Likelihood Functions
9.
Food Chem ; 366: 130600, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34311237

ABSTRACT

The effect of dual-frequency sequential ultrasonic thawing (DUT) on the quality of quick-frozen small yellow croaker was studied by TMT-labeled quantitative proteomic method. A total number of 75 proteins were identified as differentially abundant proteins (DAPs) in fish meat treated by DUT, while 72 DAPs were in flow water thawing (FWT). The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis indicated that the DAPs in the significant enrichment pathway of DUT group were enzymes. Compared with FWT, DUT had a significant effect on the enzyme content. The correlation analyses indicated that 40 DAPs were related with the quality traits. The 11 highly correlated DAPs are expected to be used as potential protein markers for texture profile analyses, color, thawing loss, water-holding capacity, and pH of thawed small yellow croaker quality. These results provide a further understanding of the quality stability of quick-frozen small yellow croaker treated by the DUT.


Subject(s)
Perciformes , Proteomics , Animals , Fishes , Genome , Meat , Perciformes/genetics
10.
Methods Mol Biol ; 2360: 1-8, 2022.
Article in English | MEDLINE | ID: mdl-34495502

ABSTRACT

MicroRNAs (miRNAs) are important regulatory noncoding RNAs (ncRNAs) at the posttranscriptional level of gene expression. Linear long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) can function as competing endogenous RNAs (ceRNAs) of miRNAs and regulate the expression of protein-coding genes. This chapter presents a procedure for the bioinformatic analysis of these three ncRNAs that are differentially expressed during insect development. In the first step, lncRNAs and circRNAs are identified based on RNA-sequencing data. In the second step, miRNAs are identified based on small RNA-sequencing data and combined with the two ncRNAs from the previous step for functional characterization.


Subject(s)
RNA, Long Noncoding/genetics , Animals , Genome , Insecta/genetics , MicroRNAs/genetics , RNA, Circular , RNA, Untranslated/genetics
11.
Methods Mol Biol ; 2377: 123-141, 2022.
Article in English | MEDLINE | ID: mdl-34709614

ABSTRACT

High-throughput genetic screens based on CRISPR/Cas9 technology are powerful tools to genome-wide identify gene function and genotype-phenotype association. Here, we describe a detailed protocol for conducting and evaluating pooled CRISPR screens interfering with gene expression in Escherichia coli. We provide step-by-step instructions for guide RNA library design and construction, genome-scale screening and next-generation sequencing data processing. This tool outperforms transposon sequencing (Tn-seq) with similar library sizes and short gene length. The workflow can be used in follow-up studies implemented in other bacteria systems.


Subject(s)
CRISPR-Cas Systems , Bacteria , CRISPR-Cas Systems/genetics , Genome , Genome, Bacterial , Genomics , RNA, Guide/genetics
12.
Methods Mol Biol ; 2301: 1-15, 2022.
Article in English | MEDLINE | ID: mdl-34415528

ABSTRACT

Over the last decade, genomic proximity ligation approaches have reshaped our vision of chromosomes 3D organizations, from bacteria nucleoids to larger eukaryotic genomes. The different protocols (3Cseq, Hi-C, TCC, MicroC [XL], Hi-CO, etc.) rely on common steps (chemical fixation digestion, ligation…) to detect pairs of genomic positions in close proximity. The most common way to represent these data is a matrix, or contact map, which allows visualizing the different chromatin structures (compartments, loops, etc.) that can be associated to other signals such as transcription, protein occupancy, etc. as well as, in some instances, to biological functions.In this chapter we present and discuss the filtering of the events recovered in proximity ligation experiments as well as the application of the balancing normalization procedure on the resulting contact map. We also describe a computational tool for visualizing normalized contact data dubbed Scalogram.The different processes described here are illustrated and supported by the laboratory custom-made scripts pooled into "hicstuff," an open-access python package accessible on github ( https://github.com/koszullab/hicstuff ).


Subject(s)
Chromosomes , Chromatin/genetics , Genome , Genomics
13.
Methods Mol Biol ; 2301: 39-59, 2022.
Article in English | MEDLINE | ID: mdl-34415530

ABSTRACT

Chromatin folding in the 3D space of the nucleus can be explored through high-throughput chromosome conformation capture (Hi-C) approaches. These experiments quantify the number of interactions between any pair of genomic loci in the genome and, thus, allow building genome-scale maps of intra- and inter-chromosomal contacts (contact maps). Statistical and algorithmic analyses of Hi-C data consist in extracting information from these contact maps. One of the most striking patterns observed in intra-chromosomal Hi-C contact maps emerged from genomic regions that exhibit dense intra-region but sparse inter-region contacts. These have been termed topologically associating domains (TADs). The identification of TADs from Hi-C contact maps is of great interest as they have been shown to act as unit of chromosome organization and, potentially, functional activity. Several approaches have been developed to identify TADs (TAD callers). However, results from these methods are often dependent on data resolution and poorly concordant. In this chapter, we present four TAD callers and we provide detailed protocols for their use. In addition, we show how to compare TADs identified by different callers and how to assess the enrichment for TAD-associated biological features. TAD calling has become a key step in the study of chromatin 3D organization in different cellular contexts. Here we provide guidelines to improve the robustness and quality of these analyses.


Subject(s)
Genomics , Cell Nucleus , Chromatin/genetics , Chromosomes/genetics , Genome
14.
Methods Mol Biol ; 2301: 61-95, 2022.
Article in English | MEDLINE | ID: mdl-34415531

ABSTRACT

The 3D organization of chromatin within the nucleus enables dynamic regulation and cell type-specific transcription of the genome. This is true at multiple levels of resolution: on a large scale, with chromosomes occupying distinct volumes (chromosome territories); at the level of individual chromatin fibers, which are organized into compartmentalized domains (e.g., Topologically Associating Domains-TADs), and at the level of short-range chromatin interactions between functional elements of the genome (e.g., enhancer-promoter loops).The widespread availability of Chromosome Conformation Capture (3C)-based high-throughput techniques has been instrumental in advancing our knowledge of chromatin nuclear organization. In particular, Hi-C has the potential to achieve the most comprehensive characterization of chromatin 3D interactions, as it is theoretically able to detect any pair of restriction fragments connected as a result of ligation by proximity.This chapter will illustrate how to compare the chromatin interactome in different experimental conditions, starting from pre-computed Hi-C contact matrices, how to visualize the results, and how to correlate the observed variations in chromatin interaction strength with changes in gene expression.


Subject(s)
Genome , Cell Nucleus/genetics , Chromatin/genetics , Chromatin Assembly and Disassembly , Chromosomes/genetics , Software
15.
Methods Mol Biol ; 2301: 97-132, 2022.
Article in English | MEDLINE | ID: mdl-34415532

ABSTRACT

Epigenomics studies require the combined analysis and integration of multiple types of data and annotations to extract biologically relevant information. In this context, sophisticated data visualization techniques are fundamental to identify meaningful patterns in the data in relation to the genomic coordinates. Data visualization for Hi-C contact matrices is even more complex as each data point represents the interaction between two distant genomic loci and their three-dimensional positioning must be considered. In this chapter we illustrate how to obtain sophisticated plots showing Hi-C data along with annotations for other genomic features and epigenomics data. For the example code used in this chapter we rely on a Bioconductor package able to handle even high-resolution Hi-C datasets. The provided examples are explained in details and highly customizable, thus facilitating their extension and adoption by end users for other studies.


Subject(s)
Software , Chromatin , Epigenomics , Genome , Genomics
16.
Methods Mol Biol ; 2301: 143-161, 2022.
Article in English | MEDLINE | ID: mdl-34415534

ABSTRACT

Structural variations (SVs) are large genomic rearrangements that can be challenging to identify with current short read sequencing technology due to various confounding factors such as existence of genomic repeats and complex SV structures. Hi-C breakfinder is the first computational tool that utilizes the technology of high-throughput chromatin conformation capture assay (Hi-C) to systematically identify SVs, without being interfered by regular confounding factors. SVs change the spatial distance of genomic regions and cause discontinuous signals in Hi-C, which are difficult to analyze by routine informatics practice. Here we provide step-by-step guidance for how to identify SVs using Hi-C data and how to reconstruct Hi-C maps in the presence of SVs.


Subject(s)
Genomics , Neoplasms , Chromatin , Chromosomes , Genome , High-Throughput Nucleotide Sequencing , Humans , Neoplasms/genetics , Software
17.
Methods Mol Biol ; 2301: 337-352, 2022.
Article in English | MEDLINE | ID: mdl-34415545

ABSTRACT

The three-dimensional (3D) organization of the genome is shaped by interactions with multiple structures within the nucleus, affecting gene expression outcomes. Technological breakthroughs in recent years have generated vast data reflecting various aspects of nuclear genome architecture in space and time. Integrating these datasets into comprehensive 3D genome models can reveal new insights into genome structure and regulation in normal and disease states. In this chapter, we provide a step-by-step guide on how to generate publication-ready integrated 3D genome models from (raw) Hi-C data and from lamin-genome (LAD) contacts.


Subject(s)
Genome , Nuclear Lamina , Cell Nucleus/genetics , Chromatin , Lamins
18.
New Phytol ; 233(1): 555-568, 2022 01.
Article in English | MEDLINE | ID: mdl-34637540

ABSTRACT

Natural selection shapes genome-wide patterns of diversity within species and divergence between species. However, quantifying the efficacy of selection and elucidating the relative importance of different types of selection in shaping genomic variation remain challenging. We sequenced whole genomes of 101 individuals of three closely related oak species to track the divergence history, and to dissect the impacts of selective sweeps and background selection on patterns of genomic variation. We estimated that the three species diverged around the late Neogene and experienced a bottleneck during the Pleistocene. We detected genomic regions with elevated relative differentiation ('FST -islands'). Population genetic inferences from the site frequency spectrum and ancestral recombination graph indicated that FST -islands were formed by selective sweeps. We also found extensive positive selection; the fixation of adaptive mutations and reduction neutral diversity around substitutions generated a signature of selective sweeps. Prevalent negative selection and background selection have reduced genetic diversity in both genic and intergenic regions, and contributed substantially to the baseline variation in genetic diversity. Our results demonstrate the importance of linked selection in shaping genomic variation, and illustrate how the extent and strength of different selection models vary across the genome.


Subject(s)
Quercus , Genetic Variation , Genetics, Population , Genome , Genomics , Quercus/genetics , Selection, Genetic
19.
Methods Mol Biol ; 2349: 339-365, 2022.
Article in English | MEDLINE | ID: mdl-34719002

ABSTRACT

COBRA toolbox is one of the most popular tools for systems biology analyses using genome-scale metabolic reconstructions. The toolbox permits the use of many constraint-based analytical methods for examining characteristics of metabolism in the biosystems ranging in complexity from single cells to microbial communities and ultimately multicellular organisms. The toolbox has a number of different variants that can be used depending on a user's choice of programming language. Here, I provide a basic tutorial for beginners that plan to use the original MATLAB version of the toolbox.


Subject(s)
Metabolic Networks and Pathways , Software , Genome , Models, Biological , Programming Languages , Systems Analysis
20.
Methods Mol Biol ; 2349: 321-338, 2022.
Article in English | MEDLINE | ID: mdl-34719001

ABSTRACT

Constraint-based reconstruction and analysis (COBRA) methods have been used for over 20 years to generate genome-scale models of metabolism in biological systems. The COBRA models have been utilized to gain new insights into the biochemical conversions that occur within organisms and allow their survival and proliferation. Using these models, computational biologists can conduct a variety of different analyses such as examining network structures, predicting metabolic capabilities, resolving unexplained experimental observations, generating and testing new hypotheses, assessing the nutritional requirements of a biosystem and approximating its environmental niche, identifying missing enzymatic functions in the annotated genomes, and engineering desired metabolic capabilities in model organisms. This chapter details the protocol for developing curated system-level COBRA models of metabolism in microbes.


Subject(s)
Computational Biology , Microbiological Phenomena , Genome , Metabolic Networks and Pathways , Models, Biological
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