Efficient randomization of biological networks while preserving functional characterization of individual nodes

AbstractBackgroundNetworks are popular and powerful tools to describe and model biological processes. Many computational methods have been developed to infer biological networks from literature, high-throughput experiments, and combinations of both. Additionally, a wide range of tools has been developed to map experimental data onto reference biological networks, in order to extract meaningful modules. Many of these methods assess results’ significance against null distributions of randomized networks. However, these standard unconstrained randomizations do not preserve the functional characterization of the nodes in the reference networks (i.e. their degrees and connection signs), hence including potential biases in the assessment.ResultsBuilding on our previous work about rewiring bipartite networks, we propose a method for rewiring any type of unweighted networks. In particular we formally demonstrate that the problem of rewiring a signed and directed network preserving its functional connectivity (F-rewiring) reduces to the problem of rewiring two induced bipartite networks. Additionally, we reformulate the lower bound to the iterations’ number of the switching-algorithm to make it suitable for the F-rewiring of networks of any size. Finally, we present BiRewire 3, an open-source Bioconductor software enabling the F-rewiring of any type of unweighted network. We illustrate its application to a case study about the identification of modules from gene expression data mapped on protein interaction networks, and a second one focused on building logic models from more complex signed-directed reference signaling networks and phosphoproteomic data.ConclusionsBiRewire3 it is freely available at https://www.bioconductor.org/packages/BiRewire/, and it should have a broad application as it allows an efficient and analytically derived statistical assessment of results from any network biology tool.

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Efficient randomization of biological networks while preserving functional characterization of individual nodes

BMC Bioinformatics ◽

10.1186/s12859-016-1402-1 ◽

2016 ◽

Vol 17 (1) ◽

Cited By ~ 12

Author(s):

Francesco Iorio ◽

Marti Bernardo-Faura ◽

Andrea Gobbi ◽

Thomas Cokelaer ◽

Giuseppe Jurman ◽

...

Keyword(s):

Biological Networks ◽

Functional Characterization ◽

Individual Nodes

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Plugging Small RNAs into the Network

mSystems ◽

10.1128/msystems.00422-20 ◽

2020 ◽

Vol 5 (3) ◽

Author(s):

Lars Barquist

Keyword(s):

Small Rnas ◽

Posttranscriptional Regulation ◽

Network Inference ◽

Functional Characterization ◽

The State ◽

Diverse Range ◽

Regulatory Interactions ◽

Link Type ◽

Wide Range

ABSTRACT Small RNAs (sRNAs) have been discovered in every bacterium examined and have been shown to play important roles in the regulation of a diverse range of behaviors, from metabolism to infection. However, despite a wide range of available techniques for discovering and validating sRNA regulatory interactions, only a minority of these molecules have been well characterized. In part, this is due to the nature of posttranscriptional regulation: the activity of an sRNA depends on the state of the transcriptome as a whole, so characterization is best carried out under the conditions in which it is naturally active. In this issue of mSystems, Arrieta-Ortiz and colleagues (M. L. Arrieta-Ortiz, C. Hafemeister, B. Shuster, N. S. Baliga, et al., mSystems 5:e00057-20, 2020, https://doi.org/10.1128/mSystems.00057-20) present a network inference approach based on estimating sRNA activity across transcriptomic compendia. This shows promise not only for identifying new sRNA regulatory interactions but also for pinpointing the conditions in which these interactions occur, providing a new avenue toward functional characterization of sRNAs.

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Proteomics Strategy for Identifying Candidate Bioactive Proteins in Complex Mixtures: Application to the Platelet Releasate

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/107859 ◽

2010 ◽

Vol 2010 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Roisin O'Connor ◽

Lorna M. Cryan ◽

Kieran Wynne ◽

Andreas de Stefani ◽

Desmond Fitzgerald ◽

...

Keyword(s):

Ion Exchange ◽

Functional Characterization ◽

Biological Tissues ◽

Biochemical Properties ◽

Human Platelets ◽

Intact Proteins ◽

Large Numbers ◽

Wide Range ◽

Platelet Releasate

Proteomic approaches have proven powerful at identifying large numbers of proteins, but there are fewer reports of functional characterization of proteins in biological tissues. Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity to identity. We used consecutive orthogonal separation platforms to ensure sensitive detection: (a) ion-exchange of intact proteins, (b) SDS-PAGE separation of ion-exchange fractions and (c) HPLC separation of tryptic digests coupled to electrospray tandem mass spectrometry. Migration of THP-1 monocytes in response to complete or fractionated platelet releasate was assessed and located to just one of the forty-nine ion-exchange fractions. Over 300 proteins were identified in the releasate, with a wide range of annotated biophysical and biochemical properties, in particular platelet activation, adhesion, and wound healing. The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western blotting. Proteins identified within the fraction with monocyte promigratory activity and not in other inactive fractions included vimentin, PEDF, and TIMP-1. We conclude that this analytical platform is effective for the characterization of complex bioactive samples.

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Characterization of PPTNs, a Cyanobacterial Phosphopantetheinyl Transferase from Nodularia spumigena NSOR10

Journal of Bacteriology ◽

10.1128/jb.01850-06 ◽

2007 ◽

Vol 189 (8) ◽

pp. 3133-3139 ◽

Cited By ~ 19

Author(s):

J. N. Copp ◽

A. A. Roberts ◽

M. A. Marahiel ◽

B. A. Neilan

Keyword(s):

Acyl Carrier Protein ◽

Functional Characterization ◽

Bioactive Metabolites ◽

Sequence Motifs ◽

Phosphopantetheinyl Transferase ◽

Carrier Proteins ◽

Nodularia Spumigena ◽

Conserved Sequence ◽

Wide Range

ABSTRACT The phosphopantetheinyl transferases (PPTs) are a superfamily of essential enzymes required for the synthesis of a wide range of compounds, including fatty acids, polyketides, and nonribosomal peptide metabolites. These enzymes activate carrier proteins in specific biosynthetic pathways by transfer of a phosphopantetheinyl moiety. The diverse PPT superfamily can be divided into two families based on specificity and conserved sequence motifs. The first family is typified by the Escherichia coli acyl carrier protein synthase (AcpS), which is involved in fatty acid synthesis. The prototype of the second family is the broad-substrate-range PPT Sfp, which is required for surfactin biosynthesis in Bacillus subtilis. Most cyanobacteria do not encode an AcpS-like PPT, and furthermore, some of their Sfp-like PPTs belong to a unique phylogenetic subgroup defined by the PPTs involved in heterocyst differentiation. Here, we describe the first functional characterization of a cyanobacterial PPT based on a structural analysis and subsequent functional analysis of the Nodularia spumigena NSOR10 PPT. Southern hybridizations suggested that this enzyme may be the only PPT encoded in the N. spumigena NSOR10 genome. Expression and enzyme characterization showed that this PPT was capable of modifying carrier proteins resulting from both heterocyst glycoplipid synthesis and nodularin toxin synthesis. Cyanobacteria are a unique and vast source of bioactive metabolites; therefore, an understanding of cyanobacterial PPTs is important in order to harness the biotechnological potential of cyanobacterial natural products.

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Structural and functional characterization of TesB fromYersinia pestisreveals a unique octameric arrangement of hotdog domains

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s1399004715002527 ◽

2015 ◽

Vol 71 (4) ◽

pp. 986-995 ◽

Cited By ~ 5

Author(s):

C. M. D. Swarbrick ◽

M. A. Perugini ◽

N. Cowieson ◽

J. K. Forwood

Keyword(s):

Analytical Ultracentrifugation ◽

Quaternary Structure ◽

Functional Characterization ◽

Fatty Acyl ◽

Size Exclusion ◽

X Ray Scattering ◽

Wide Range ◽

Exclusion Chromatography ◽

Enzyme Families

Acyl-CoA thioesterases catalyse the hydrolysis of the thioester bonds present within a wide range of acyl-CoA substrates, releasing free CoASH and the corresponding fatty-acyl conjugate. The TesB-type thioesterases are members of the TE4 thioesterase family, one of 25 thioesterase enzyme families characterized to date, and contain two fused hotdog domains in both prokaryote and eukaryote homologues. Only two structures have been elucidated within this enzyme family, and much of the current understanding of the TesB thioesterases has been based on theEscherichia colistructure.Yersinia pestis, a highly virulent bacterium, encodes only one TesB-type thioesterase in its genome; here, the structural and functional characterization of this enzyme are reported, revealing unique elements both within the protomer and quaternary arrangements of the hotdog domains which have not been reported previously in any thioesterase family. The quaternary structure, confirmed using a range of structural and biophysical techniques including crystallography, small-angle X-ray scattering, analytical ultracentrifugation and size-exclusion chromatography, exhibits a unique octameric arrangement of hotdog domains. Interestingly, the same biological unit appears to be present in both TesB structures solved to date, and is likely to be a conserved and distinguishing feature of TesB-type thioesterases. Analysis of theY. pestisTesB thioesterase activity revealed a strong preference for octanoyl-CoA and this is supported by structural analysis of the active site. Overall, the results provide novel insights into the structure of TesB thioesterases which are likely to be conserved and distinguishing features of the TE4 thioesterase family.

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Simplified Computational Model for Generating Biological Networks

10.26434/chemrxiv.12662240.v1 ◽

2020 ◽

Author(s):

Matthew Bailey ◽

David Ormrod Morley ◽

Mark Wilson

Keyword(s):

Computational Model ◽

Network Structure ◽

Biological Networks ◽

Full Range ◽

Node Degree ◽

Switching Algorithm ◽

Local Ordering ◽

Wide Range ◽

Analogous Manner ◽

The Mean

A method to generate and simulate biological networks is discussed. An expanded Wooten-Winer-Weaire bond switching methodsis proposed which allows fora distribution of node degrees in the network while conserving the mean average node degree.The networks are characterised in terms of their polygon structure and assortativities (a measureof local ordering). A wide range of experimental images are analysed and the underlying networksquantified in an analogous manner. Limitations in obtaining the network structure are discussed.A "network landscape" of the experimentally observed and simulated networks is constructed from the underlying metrics.The enhanced bond switching algorithm is able to generate networks spanning the full range of experimental observations.

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Genome-Wide Identification and Functional Characterization of the Trans-Isopentenyl Diphosphate Synthases Gene Family in Cinnamomum camphora

Frontiers in Plant Science ◽

10.3389/fpls.2021.708697 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zerui Yang ◽

Chunzhu Xie ◽

Ting Zhan ◽

Linhuan Li ◽

Shanshan Liu ◽

...

Keyword(s):

Essential Oil ◽

Gene Family ◽

Functional Characterization ◽

Cinnamomum Camphora ◽

Isopentenyl Diphosphate ◽

Geranyl Diphosphate ◽

Wide Range ◽

Camphor Tree

Trans-isopentenyl diphosphate synthases (TIDSs) genes are known to be important determinants for terpene diversity and the accumulation of terpenoids. The essential oil of Cinnamomum camphora, which is rich in monoterpenes, sesquiterpenes, and other aromatic compounds, has a wide range of pharmacological activities and has therefore attracted considerable interest. However, the TIDS gene family, and its relationship to the camphor tree (C. camphora L. Presl.), has not yet been characterized. In this study, we identified 10 TIDS genes in the genome of the C. camphora borneol chemotype that were unevenly distributed on chromosomes. Synteny analysis revealed that the TIDS gene family in this species likely expanded through segmental duplication events. Furthermore, cis-element analyses demonstrated that C. camphora TIDS (CcTIDS) genes can respond to multiple abiotic stresses. Finally, functional characterization of eight putative short-chain TIDS proteins revealed that CcTIDS3 and CcTIDS9 exhibit farnesyl diphosphate synthase (FPPS) activity, while CcTIDS1 and CcTIDS2 encode geranylgeranyl diphosphate synthases (GGPPS). Although, CcTIDS8 and CcTIDS10 were found to be catalytically inactive alone, they were able to bind to each other to form a heterodimeric functional geranyl diphosphate synthase (GPPS) in vitro, and this interaction was confirmed using a yeast two-hybrid assay. Furthermore, transcriptome analysis revealed that the CcTIDS3, CcTIDS8, CcTIDS9, and CcTIDS10 genes were found to be more active in C. camphora roots as compared to stems and leaves, which were verified by quantitative real-time PCR (qRT-PCR). These novel results provide a foundation for further exploration of the role of the TIDS gene family in camphor trees, and also provide a potential mechanism by which the production of camphor tree essential oil could be increased for pharmacological purposes through metabolic engineering.

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Structural and functional characterization of human and murine C5a anaphylatoxins

Acta Crystallographica Section D Biological Crystallography ◽

10.1107/s139900471400844x ◽

2014 ◽

Vol 70 (6) ◽

pp. 1704-1717 ◽

Cited By ~ 17

Author(s):

Janus Asbjørn Schatz-Jakobsen ◽

Laure Yatime ◽

Casper Larsen ◽

Steen Vang Petersen ◽

Andreas Klos ◽

...

Keyword(s):

Complement Activation ◽

Functional Characterization ◽

Functional Assay ◽

Helix Bundle ◽

Wide Range ◽

A Cell ◽

Four Helix Bundle ◽

G Protein Coupled

Complement is an ancient part of the innate immune system that plays a pivotal role in protection against invading pathogens and helps to clear apoptotic and necrotic cells. Upon complement activation, a cascade of proteolytic events generates the complement effectors, including the anaphylatoxins C3a and C5a. Signalling through their cognate G-protein coupled receptors, C3aR and C5aR, leads to a wide range of biological events promoting inflammation at the site of complement activation. The function of anaphylatoxins is regulated by circulating carboxypeptidases that remove their C-terminal arginine residue, yielding C3a-desArg and C5a-desArg. Whereas human C3a and C3a-desArg adopt a canonical four-helix bundle fold, the conformation of human C5a-desArg has recently been described as a three-helix bundle. Here, the crystal structures of an antagonist version of human C5a, A8Δ71–73, and of murine C5a and C5a-desArg are reported. Whereas A8Δ71–73adopts a three-helix bundle conformation similar to human C5a-desArg, the two murine proteins form a four-helix bundle. A cell-based functional assay reveals that murine C5a-desArg, in contrast to its human counterpart, exerts the same level of activition as murine C5a on its cognate receptor. The role of the different C5a conformations is discussed in relation to the differential activation of C5a receptors across species.

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Functional Characterization of BrF3'H, Which Determines the Typical Flavonoid Profile of Purple Chinese Cabbage

Frontiers in Plant Science ◽

10.3389/fpls.2021.793589 ◽

2021 ◽

Vol 12 ◽

Author(s):

Sangkyu Park ◽

Hyo Lee ◽

Myung Ki Min ◽

Jihee Ha ◽

Jaeeun Song ◽

...

Keyword(s):

Chinese Cabbage ◽

Expression Patterns ◽

Functional Characterization ◽

Phenylpropanoid Pathway ◽

Amino Acid Sequences ◽

In Planta ◽

Normal Green ◽

Wide Range

Flavonols and anthocyanins are the two major classes of flavonoids in Brassica rapa. To elucidate the flavonoid biosynthetic pathway in Chinese cabbage (B. rapa L. subsp. pekinensis), we analyzed flavonoid contents in two varieties of Chinese cabbage with normal green (5546) and purple (8267) leaves. The 8267 variety accumulates significantly higher levels of quercetin, isorhamnetin, and cyanidin than the 5546 variety, indicating that 3′-dihydroxylated flavonoids are more prevalent in the purple than in the green variety. Gene expression analysis showed that the expression patterns of most phenylpropanoid pathway genes did not correspond to the flavonoid accumulation patterns in 5546 and 8267 varieties, except for BrPAL1.2 while most early and late flavonoid biosynthetic genes are highly expressed in 8267 variety. In particular, the flavanone 3′-hydroxylase BrF3′H (Bra009312) is expressed almost exclusively in 8267. We isolated the coding sequences of BrF3′H from the two varieties and found that both sequences encode identical amino acid sequences and are highly conserved with F3'H genes from other species. An in vitro enzymatic assay demonstrated that the recombinant BrF3′H protein catalyzes the 3′-hydroxylation of a wide range of 4′-hydroxylated flavonoid substrates. Kinetic analysis showed that kaempferol is the most preferred substrate and dihydrokaempferol (DHK) is the poorest substrate for recombinant BrF3′H among those tested. Transient expression of BrF3′H in Nicotiana benthamiana followed by infiltration of naringenin and DHK as substrates resulted in eriodictyol and quercetin production in the infiltrated leaves, demonstrating the functionality of BrF3′H in planta. As the first functional characterization of BrF3′H, our study provides insight into the molecular mechanism underlying purple coloration in Chinese cabbage.

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Recent Advances in Camel Immunology

Frontiers in Immunology ◽

10.3389/fimmu.2020.614150 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jamal Hussen ◽

Hans-Joachim Schuberth

Keyword(s):

Cytotoxic T Cells ◽

Functional Characterization ◽

Desert Ecosystem ◽

Physiological Age ◽

Cellular Immunology ◽

Wide Range ◽

Innate Recognition ◽

Antigen Presenting ◽

The Impact

Camels are domesticated animals that are highly adapted to the extreme desert ecosystem with relatively higher resistance to a wide range of pathogens compared to many other species from the same geographical region. Recently, there has been increased interest in the field of camel immunology. As the progress in the analysis of camel immunoglobulins has previously been covered in many recent reviews, this review intends to summarize published findings related to camel cellular immunology with a focus on the phenotype and functionality of camel leukocyte subpopulations. The review also describes the impact of different physiological (age and pregnancy) and pathological (e.g. infection) conditions on camel immune cells. Despite the progress achieved in the field of camel immunology, there are gaps in our complete understanding of the camel immune system. Questions remain regarding innate recognition mechanisms, the functional characterization of antigen-presenting cells, and the characterization of camel NK and cytotoxic T cells.

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