Biology subjects

Berry, A.

Publications and source records attributed to Berry, A..

16 recordsLinked to original sources

bioRxiv2026

Single-cell characterization of the human immune landscape reveals dysfunction in monocyte-mediated cellular interactions in symptomatic malaria

Plasmodium falciparum infection results in a wide range of phenotypes including chronic asymptomatic and symptomatic individuals. The malaria outcome depends, at least in part, on host immune responses mediated by specific cell subsets. Here, we investigated the immune landscape of chronic asymptomatic and symptomatic children using single-cell RNA sequencing. Unexpectedly, we uncovered biologically relevant immune cell complexes, which were further confirmed by imaging flow cytometry. Symptomatic infection was associated with a decrease of cell-cell interactions, particularly between non-classical monocytes and T cells. Non-classical monocytes from symptomatic children exhibited profiles with increased inflammation characterized by enhanced S100A8-S100A9 expression together with decreased expression of interaction-associated genes such as CD86 or ITGAL. Moreover, we demonstrated that inflammatory and cell interaction programs could not be activated simultaneously within the same cell. In addition, the concomitant expression of inflammatory genes and members of the LILR gene family was predominantly observed in monocytes from symptomatic individuals. These findings raise the possibility that enhanced S100A8/S100A9-LILRB1 signaling may contribute to the altered functional state of monocytes in symptomatic malaria and, potentially, may impair their interactions with T cells. Together, our results suggest that immune cell complexes may therefore reveal an additional layer of immune regulation associated with the development of clinical malaria.

genomics↗

bioRxiv2026

Big-team science reveals that patterns of inhibitory control variation in teleost fishes differ from those in mammals and birds

Understanding the evolution of cognition is fundamental to understanding the origins and nature of our own cognitive abilities, with cross-species comparisons providing a cornerstone of this endeavor. Yet, comparative cognition so far has largely focused on endothermic vertebrates, particularly mammals and birds, while ectotherms--representing a substantial proportion of vertebrate diversity--remain relatively understudied. Moreover, variation in experimental methods makes existing data difficult to compare across species. Big-team science offers a way to overcome these limitations by enabling standardized cognitive testing across broad taxonomic scales. Here, we apply this approach to fishes, using inhibitory control as a proof of concept for standardized comparative testing in 444 individuals across 22 teleost species spanning 19 genera. We demonstrate that standardized cognitive testing across such diversity is feasible, while also revealing substantial heterogeneity in the sample. Performance varied markedly among species, but, strikingly, showed only a weak phylogenetic signal, contrasting with patterns previously reported in mammals and birds. In addition, we detected great within-species variation, including differences across research groups, suggesting that performance may reflect not only species-level evolutionary history but also ontogenetic experience and the capacity to adjust decision rules to local conditions. Together, our findings highlight the importance of both evolutionary and environmental sources of cognitive variation and demonstrate that extending standardized comparative approaches beyond traditionally studied endotherms can reveal a more dynamic and complex picture of cognitive evolution across the vertebrate lineage.

animal behavior and cognition↗

bioRxiv2025

Cortical Iron in Schizophrenia: A Quantitative Susceptibility Mapping and Diffusion Tensor Imaging MRI Study

Background and HypothesisCognitive and negative symptoms in schizophrenia remain poorly treated. Iron dysregulation has been implicated as a potential mechanism underlying cognitive dysfunction and schizophrenia. While elevated postmortem iron in Brodmann areas 10-11 has been linked to schizophrenia, this has not been assessed in vivo. We therefore used iron-sensitive MRI to test whether cortical iron is elevated in individuals with schizophrenia compared to healthy controls. Study DesignWe acquired quantitative susceptibility mapping (QSM) MRI to measure magnetic susceptibility ({chi}), a marker of iron, in 158 participants aged 18-45 (73 with schizophrenia and 76 matched healthy controls). As {chi} is reduced by myelin, we conducted diffusion tensor imaging (DTI) to assess mean diffusivity, an iron-insensitive marker also reduced by myelin. Study ResultsPrimary analyses showed no significant case-control differences in {chi} in the whole cortex (p=0.675) or Brodmann areas 10-11 (p=0.537). Exploratory analyses examined {chi} for 362 cortical regions and a voxelwise analysis, correcting for multiple comparisons. Two left temporo-parieto-occipital (TPO) junction regions showed significantly elevated {chi} in schizophrenia: the posterior TPO junction (d=0.752, p<0.001) and the superior temporal visual area (d=0.638, p=0.033), which remained significant after adjusting for mean diffusivity and clinical covariates (p=0.001 and p=0.023, respectively). Voxelwise analysis confirmed elevated {chi} in schizophrenia in the left TPO junction (peak t=5.62). ConclusionsThis study provides the first in vivo evidence of elevated cortical iron in schizophrenia, suggesting regional iron accumulation may contribute to cortical pathology.

neuroscience↗

bioRxiv2024

GENCODE: massively expanding the lncRNA catalog through capture long-read RNA sequencing

Accurate and complete gene annotations are indispensable for understanding how genome sequences encode biological functions. For more than twenty years, the GENCODE consortium has developed reference annotations for the human and mouse genomes, becoming a foundation for biomedical and genomics communities worldwide. Nevertheless, collections of important yet poorly-understood gene classes like long non-coding RNAs (lncRNAs) remain incomplete and scattered across multiple, uncoordinated catalogs. To address this, GENCODE has undertaken the most comprehensive lncRNA annotation effort to date. This is founded on the manually supervised computational annotation of full-length targeted long-read sequencing, on matched embryonic and adult tissues, of orthologous regions in human and mouse. Altogether 17,931 human genes (140,268 transcripts) and 22,784 mouse genes (136,169 transcripts) have been added to the GENCODE catalog representing a 2-fold and 6-fold growth in transcripts, respectively - the greatest increase in the number of annotated human genes since the sequencing of the human genome. Our targeted design assigned human-mouse orthologs at a rate beyond previous studies, tripling the number of human disease-associated lncRNAs that have mouse orthologs. Novel lncRNA genes consistently exhibit biological signals of functionality, and they greatly enhance the functional interpretability of the human genome. While poorly expressed in bulk RNA-Seq samples, many of them are highly expressed in specific cell populations, maybe even contributing to cell-type determination. The expanded GENCODE lncRNA annotations mark a critical step toward deciphering the human and mouse genomes.

genomics↗

bioRxiv2024

Bacteria-phage (co)evolution is constrained in a synthetic community across multiple bacteria-phage pairs

Bacteriophages can be important drivers of bacterial densities, and therefore microbial community composition and function. These ecological interactions are likely to be greatly affected by evolutionary dynamics, because bacteria can rapidly evolve resistance to phage while phage can reciprocally evolve to increase infectivity. Most studies to date have explored eco-evolutionary dynamics using isolated pairs of bacteria-phage but in nature, multiple bacteria and phages coexist and (co)evolve simultaneously. How coevolution plays out in this context is poorly understood. Here, we examine how three coexisting soil bacteria (Ochrobactrum sp., Pseudomonas sp., and Variovorax sp.) interact and evolve with three species-specific bacteriophages over eight weeks of experimental evolution, both as host-parasite pairs in isolation and as a mixed community. Across all species phage resistance evolution was inhibited in polyculture, with the most pronounced effect on Ochrobactrum. Between bacteria-phage pairs there were also substantial differences in the effect of phage on host densities, and evolutionary dynamics including whether pairs coevolved. These contrasts emphasise the difficulty in generalising from monoculture to polyculture, and between bacteria-phage pairs to wider systems. Future studies should consider how multiple bacteria and phage pairs interact simultaneously to better understand how coevolutionary dynamics happen in natural communities. ImportanceThis project is unique in examining evolutionary dynamics among coexisting bacteria and their phages, rather than focus on single focal species - this makes our work more applicable to natural contexts while still working with controlled synthetic communities. While it is commonly assumed that bacteria will evolve phage resistance and coevolve with phage, this may be uncommon in more complex communities due to reduced contact rates and/or reduced mutation rates. Furthermore, the contrast in population dynamics and ability to coevolve between bacteria-phage pairs highlights the need for more pairs to be studied. Over-reliance on model systems that are known to coevolve means we lack an understanding of how wider bacteria-phage pairs interact, and to what extent results can be generalised beyond these pairs.

evolutionary biology↗

bioRxiv2024

Genomic exploration of the complex journey of Plasmodium vivax in Latin America

Plasmodium vivax, the predominant malaria parasite in Latin America, has a rich and complex colonization history in the region, with debated hypotheses about its origin. Our study employed cutting-edge population genomic techniques, to collect whole genome sequencing data from 620 P. vivax isolates, including 107 newly sequenced samples, thus representing nearly all potential source populations worldwide. Analyses of the genetic structure, diversity, ancestry, and also, coalescent-based inferences and scenario testing using Approximate Bayesian Computation, have revealed a more complex evolutionary history than previously envisioned. Indeed, according to our analysis, the current American P. vivax populations predominantly stemmed from a now-extinct European lineage, with the potential contribution also from unsampled populations, most likely of West African origin, during post-colonial human migration waves in the late 19th-century. This study provides a fresh perspective on P. vivax intricate evolutionary journey and brings insights into the possible contribution of West African P. vivax populations to the colonization history of Latin America.

genomics↗

bioRxiv2022

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and non-users

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine neurotransmission. Yet little is known about hormonal regulation of the dopamine system in the human brain. Using Positron Emission Tomography (PET), we address this gap by comparing hormonal contraceptive users and non-users across multiple aspects of dopamine function: dopamine synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and dopamine release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n=21 naturally cycling; n=15 hormonal contraceptive users), and men (n=20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater dopamine synthesis capacity than naturally cycling participants, particularly in dorsal caudate, and greater cognitive flexibility. Further, across individuals the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or dopamine release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to womens hormone status. Hormonal contraception (in the form of pill, shot, implant, ring or IUD) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the dopamine system. Findings from this study begin to address this critical gap in womens health.

neuroscience↗

bioRxiv2021

Rapid blood acid-base regulation by European sea bass (Dicentrarchus labrax) in response to sudden exposure to high environmental CO2

Fish in coastal ecosystems can be exposed to acute variations in CO2 that can approach 1 kPa CO2 (10,000 atm). Coping with this environmental challenge will depend on the ability to rapidly compensate the internal acid-base disturbance caused by sudden exposure to high environmental CO2 (blood and tissue acidosis); however, studies about the speed of acid-base regulatory responses in marine fish are scarce. We observed that upon exposure to ~1 kPa CO2, European sea bass (Dicentrarchus labrax) completely regulate erythrocyte intracellular pH within ~40 minutes, thus restoring haemoglobin-O2 affinity to pre-exposure levels. Moreover, blood pH returned to normal levels within ~2 hours, which is one of the fastest acid-base recoveries documented in any fish. This was achieved via a large upregulation of net acid excretion and accumulation of HCO3- in blood, which increased from ~4 to ~22 mM. While the abundance and intracellular localisation of gill Na+/K+-ATPase (NKA) and Na+/H+ exchanger 3 (NHE3) remained unchanged, the apical surface area of acid-excreting gill ionocytes doubled. This constitutes a novel mechanism for rapidly increasing acid excretion during sudden blood acidosis. Rapid acid-base regulation was completely prevented when the same high CO2 exposure occurred in seawater with experimentally reduced HCO3- and pH, likely because reduced environmental pH inhibited gill H+ excretion via NHE3. The rapid and robust acid-base regulatory responses identified will enable European sea bass to maintain physiological performance during large and sudden CO2 fluctuations that naturally occur in coastal environments. Summary statementEuropean sea bass exposed to 1 kPa (10,000 atm) CO2 regulate blood and red cell pH within 2 hours and 40 minutes, respectively, protecting O2 transport capacity, via enhanced gill acid excretion.

physiology↗

bioRxiv2019

A virus hosted in malaria-infected blood protects against T cell-mediated inflammatory diseases by impairing DC function in a type I IFN-dependent manner

Co-infections shape the host immune status, thereby influencing the development of inflammatory diseases, which can result in detrimental or beneficial effects. For example, co-infections with concurrent Plasmodium species can alter malaria clinical evolution and malaria infection itself has the ability to modulate autoimmune reactions but, in both cases, the underlying mechanisms remain ill-defined.\n\nHere, we demonstrate that the protective effects of certain rodent malaria strains on T cell-mediated inflammatory pathologies are due to an RNA virus co-hosted in malaria-parasitized blood. We show that live as well as extracts of blood parasitized by P. berghei K173 or P. yoelii 17X YM, confer full protection against Pb ANKA (PbA)-induced Experimental Cerebral Malaria (ECM) and MOG/CFA-induced experimental autoimmune encephalomyelitis (EAE), and that this is associated with a strong type I IFN signature. We detected the presence of a viral element, the RNA virus Lactate Dehydrogenase-elevating Virus (LDV), in the protective Plasmodium stabilates and we established that infection with LDV alone recapitulates the protective effects on ECM and EAE. In ECM, we further show that protection results from an IFN-I-mediated reduction in the abundance of splenic conventional dendritic cell and in their ability to produce the Th1-inducing IL-12p70, leading to a decrease in pathogenic CD4+ Th1 responses. In EAE, protection is achieved by IFN-I mediated blunting of IL-12 and IL-23, preventing the differentiation of IFN-{gamma}-, IL-17- and GM-CSF-producing encephalitogenic CD4+ T cells.\n\nThus, our results identify a virus that is co-hosted in several Plasmodium stabilates across the community and has major consequences on the host immune system. Moreover, our data emphasize the importance of considering concurrent infections for the understanding of autoimmunity and malaria-associated inflammatory complications.

immunology↗

bioRxiv2019

Alternative pathway androgen biosynthesis and human fetal female virilization

Androgen biosynthesis in the human fetus proceeds through the adrenal sex steroid precursor dehydroepiandrosterone, which is converted towards testosterone in the gonads, followed by further activation to 5-dihydrotestosterone in genital skin, thereby facilitating male external genital differentiation. Congenital adrenal hyperplasia due to P450 oxidoreductase deficiency results in disrupted dehydroepiandrosterone biosynthesis, explaining undervirilization in affected boys. However, many affected girls are born virilized, despite low circulating androgens. We hypothesized that this is due to a prenatally active, alternative androgen biosynthesis pathway from 17-hydroxyprogesterone to 5-dihydrotestosterone, which bypasses dehydroepiandrosterone and testosterone, with increased activity in congenital adrenal hyperplasia variants associated with 17-hydroxyprogesterone accumulation. Here we employ explant cultures of human fetal organs (adrenal, gonads, genital skin) from the major period of sexual differentiation and show that alternative pathway androgen biosynthesis is active in the fetus, as assessed by liquid chromatography-tandem mass spectrometry. We found androgen receptor expression in male and female genital skin using immunohistochemistry and demonstrated that both 5-dihydrotestosterone and adrenal explant culture supernatant induce nuclear translocation of the androgen receptor in female genital skin primary cultures. Analyzing urinary steroid excretion by gas chromatography-mass spectrometry, we show that neonates with P450 oxidoreductase deficiency produce androgens through the alternative androgen pathway during the first weeks of life. We provide quantitative in vitro evidence that the corresponding P450 oxidoreductase mutations predominantly support alternative pathway androgen biosynthesis. These results indicate a key role of alternative pathway androgen biosynthesis in the prenatal virilization of girls affected by congenital adrenal hyperplasia due to P450 oxidoreductase deficiency.\n\nSIGNIFICANCEIn the classic androgen biosynthesis pathway, testosterone is converted to 5-dihydrotestosterone, a step crucially required for normal male genital virilization. Congenital adrenal hyperplasia (CAH) due to P450 oxidoreductase deficiency (PORD) is an inborn disorder that disrupts classic androgen biosynthesis. However, some affected girls present with severe genital virilization at birth. We hypothesized that this is explained by a prenatally active, alternative biosynthesis pathway to 5-dihydrotestosterone. We show that adrenals and genital skin cooperate to produce androgens via the alternative pathway during the major period of human sexual differentiation and that neonates with PORD still produce alternative pathway androgens during the first weeks of life. This indicates that alternative pathway androgen biosynthesis drives prenatal virilization in CAH due to PORD.

developmental biology↗

bioRxiv2019

Gut microbiome features associated with Clostridium difficile colonization in puppies

In people, colonization with Clostridium difficile, the leading cause of antibiotic-associated diarrhea, has been shown to be associated with distinct gut microbial features, including reduced bacterial community diversity and depletion of key taxa. In dogs, the gut microbiome features that define C. difficile colonization are less well understood. We sought to define the gut microbiome features associated with C. difficile colonization in puppies, a population where the prevalence of C. difficile has been shown to be elevated, and to define the effect of puppy age and litter upon these features and C. difficile risk. We collected fecal samples from weaned (n=27) and unweaned (n=74) puppies from 13 litters and analyzed the effects of colonization status, age and litter on microbial diversity using linear mixed effects models.\n\nColonization with C. difficile was significantly associated with younger age, and colonized puppies had significantly decreased bacterial community diversity and differentially abundant taxa compared to non-colonized puppies, even when adjusting for age. C. difficile colonization remained associated with decreased bacterial community diversity, but the association did not reach statistical significance in a mixed effects model incorporating litter as a random effect.\n\nEven though litter explained a greater proportion (67%) of the variability in microbial diversity than colonization status, we nevertheless observed heterogeneity in gut microbial community diversity and colonization status within more than half of the litters, suggesting that the gut microbiome contributes to colonization resistance against C. difficile. The colonization of puppies with C. difficile has important implications for the potential zoonotic transfer of this organism to people. The identified associations point to mechanisms by which C. difficile colonization may be reduced.

epidemiology↗

bioRxiv2019

Cardiac structure and function in patients with schizophrenia taking antipsychotic drugs: an MRI study

Cardiovascular disease (CVD) is a major cause of excess mortality in schizophrenia. Preclinical evidence shows antipsychotics can cause myocardial fibrosis and myocardial inflammation in murine models, but it is not known if this is the case in patients. We therefore set out to determine if there is evidence of cardiac fibrosis and/or inflammation using cardiac MRI in medicated patients with schizophrenia compared with matched healthy controls. 31 participants (14 patients and 17 controls) underwent cardiac MRI assessing myocardial markers of fibrosis/inflammation, indexed by native myocardial T1 time, and cardiac structure (left ventricular (LV) mass) and function (left/right ventricular end-diastolic and end-systolic volumes, stroke volumes, and ejection fractions). Participants were physically fit, and matched for age, gender, smoking, blood pressure, BMI, HbA1c, ethnicity, and physical activity. Compared with controls, native myocardial T1 was significantly longer in patients with schizophrenia (effect size, d=0.89; p=0.02). Patients had significantly lower LV mass, and lower left/right ventricular end-diastolic and stroke volumes (effect sizes, d=0.86-1.08; all p-values <0.05). There were no significant differences in left/right end-systolic volumes and ejection fractions between groups (p>0.05). These results suggest an early diffuse fibro-inflammatory myocardial process in patients that is independent of established CVD-risk factors and could contribute to the excess cardiovascular mortality associated with schizophrenia. Future studies are required to determine if this is due to antipsychotic treatment or is intrinsic to schizophrenia.

physiology↗

bioRxiv2018

Novel autoregulatory cases of alternative splicing coupled with nonsense-mediated mRNA decay

Nonsense-mediated decay (NMD) is a eukaryotic mRNA surveillance system that selectively degrades transcripts with premature termination codons (PTC). Many RNA-binding proteins (RBP) regulate their expression levels by a negative feedback loop, in which RBP binds its own pre-mRNA and causes alternative splicing to introduce a PTC. We present a bioinformatic framework to identify novel such autoregulatory feedback loops by combining eCLIP assays for a large panel of RBPs with the data on shRNA inactivation of NMD pathway, and shRNA-depletion of RBPs followed by RNA-seq. We show that RBPs frequently bind their own pre-mRNAs and respond prominently to NMD pathway disruption. Poison and essential exons, i.e., exons that trigger NMD when included in the mRNA or skipped, respectively, respond oppositely to the inactivation of NMD pathway and to the depletion of their host genes, which allows identification of novel autoregulatory mechanisms for a number of human RBPs. For example, SRSF7 binds its own pre-mRNA and facilitates the inclusion of two poison exons; SFPQ binding promotes switching to an alternative distal 3-UTR that is targeted by NMD; RPS3 activates a poison 5-splice site in its pre-mRNA that leads to a frame shift; U2AF1 binding activates one of its two mutually exclusive exons, leading to NMD; TBRG4 is regulated by cluster splicing of its two essential exons. Our results indicate that autoregulatory negative feedback loop of alternative splicing and NMD is a generic form of post-transcriptional control of gene expression.

bioinformatics↗

bioRxiv2018

Insertion sequences drive the emergence of a highly adapted human pathogen

Taxonomic outliers of Pseudomonas aeruginosa of environmental origin have recently emerged as infectious for humans. Here we present the first genome-wide analysis of an isolate that caused fatal hemorrhagic pneumonia. We demonstrate that, in two sequential clones, CLJ1 and CLJ3, recovered from a patient with chronic pulmonary disease, insertion of a mobile genetic element into the P. aeruginosa chromosome affected major virulence-associated phenotypes and led to increased resistance to antibiotics used to treat the patient. Comparative proteome and transcriptome analyses revealed that this insertion sequence, ISL3, disrupted genes encoding flagellar components, type IV pili, O-specific antigens, translesion polymerase and enzymes producing hydrogen cyanide. CLJ3 possessed seven fold more IS insertions than CLJ1, some modifying its susceptibility to antibiotics by disrupting the genes for the outer-membrane porin OprD and the regulator of {beta}-lactamase expression AmpD. In the Galleria mellonella larvae model, the two strains displayed different levels of virulence, with CLJ1 being highly pathogenic. This work reveals ISs as major players in enhancing the pathogenic potential of a P. aeruginosa taxonomic outlier by modulating both, the virulence and the resistance to antimicrobials, and explains the ability of this bacterium to adapt from the environment to a human host.

microbiology↗

bioRxiv2018

Molecular basis of human asparagine synthetase inhibitor specificity

Expression of the enzyme human asparagine synthetase (ASNS) promotes metastatic progression in breast cancer, which affects L-asparagine levels and tumor cell invasiveness. Human ASNS has therefore emerged as a bona fide drug target for cancer therapy. We have reported a slow-onset, tight binding ASNS inhibitor with nanomolar affinity, but our compound exhibits poor cell permeability. On the other hand, we show here that this inhibitor exhibits remarkable selectivity for the human ASNS in HCT-116 cell lysates. By determining the first high-resolution (1.85 [A]) X-ray crystal structure for human ASNS, we have built a computational model of the enzyme complexed to our inhibitor, which provides the first insights into the intermolecular interactions mediating specificity. These findings should facilitate the development of a second generation of ASNS inhibitors, leading to the discovery of drugs to prevent metastasis.

biochemistry↗

bioRxiv2018

Healthspan pathway maps in C. elegans and humans highlight transcription, prolifera-tion/biosynthesis and lipids

The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. However, a precise definition of health and healthspan is not straightforward, and the causal molecular basis of health \"per se\" is largely unknown. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans, we compile a list of features of health and of the genes associated with them. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans, featuring the themes transcription initiation, proliferation and cholesterol/lipid processing, and for C. elegans, featuring the themes immune response, mitochondrion and biosynthesis based on genetic and compound intervention data, and lipids, biosynthesis and transcription based on WormBase compound intervention data. Overlaying healthspan-related gene expression data (describing effects of metabolic intervention associated with improvements in health) onto the aforementioned healthspan pathway maps, we observe the downregulation of Notch signalling in humans and of proliferation/cell-cycle in C. elegans. The former reflects the proinflammatory role of the Notch pathway. We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, is available as a reference for future investigations, at http://www.h2020awe.eu/index.php/pathways/.

bioinformatics↗