Biology subjects

Murphy, C.

Publications and source records attributed to Murphy, C..

35 records · Page 2Linked to original sources

bioRxiv2021

Genomes of novel Myxococcota reveal severely curtailed machineries for predation and cellular differentiation

Cultured Myxococcota are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured Myxococcota from anaerobic, non-soil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the Myxococcota from an anoxic freshwater spring in Oklahoma, USA. Compared to their soil counterparts, anaerobic Myxococcota possess smaller genomes, and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of thirteen distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g. FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine-learning approaches based on a set of 634 genes informative of social lifestyle predicted a non-social behavior for Zodletone Myxococcota. Metabolically, Zodletone Myxococcota genomes lacked aerobic respiratory capacities, but encoded genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 Mya in response to the rise of soil as a distinct habitat on earth. ImportanceThe Myxococcota is a phylogenetically coherent bacterial lineage that exhibits unique social traits. Cultured Myxococcoat are predominantly aerobic soil-dwelling microorganisms that are capable of predation and fruiting body formation. However, multiple yet-uncultured lineages within the Myxococcota has been encountered in a wide range of non-soil, predominantly anaerobic habitats; and the metabolic capabilities, physiological preferences, and capacity of social behavior of such lineages remains unclear. Here, we analyzed genomes recovered from a metagenomic analysis of an anoxic freshwater spring in Oklahoma, USA that represent novel, yet-uncultured, orders and families in the Myxococcota. The genomes appear to lack the characteristic hallmarks for social behavior encountered in Myxococcota genomes, and displayed a significantly smaller genome size and a smaller number of genes encoding biosynthetic gene clusters, peptidases, signal transduction systems, and transcriptional regulators. Such perceived lack of social capacity we confirmed through detailed comparative genomic analysis of thirteen pathways associated with Myxococcota social behavior, as well as the implementation of machine learning approaches to predict social behavior based on genome composition. Metabolically, these novel Myxococcota are predicted to be strict anaerobes, utilizing fermentation, nitrate rductio, and dissimilarity sulfate reduction for energy acquisition. Our result highlight the broad patterns of metabolic diversity within the yet-uncultured Myxococcota and suggest that the evolution of predation and fruiting body formation in the Myxococcoat has occurred in response to soil formation as a distinct habitat on earth.

microbiology↗

bioRxiv2021

Microbial diversity and sulfur cycling in an early earth analogue: From ancient novelty to modern commonality

Life emerged and diversified in the absence of molecular oxygen. The prevailing anoxia and unique sulfur chemistry in the Paleo-, Meso- and Neoarchean, and early Proterozoic eons may have supported microbial communities that are drastically different than those currently thriving on the earths surface. Zodletone spring in southwestern Oklahoma represents a unique habitat where spatial sampling could substitute for geological eons: from the anoxic, surficial light exposed sediments simulating a preoxygenated earth, to overlaid water column where air exposure simulates the relentless oxygen intrusion during the Neo Proterozoic. We document a remarkably diverse microbial community in the anoxic spring sediments, with 340/516 (65.89%) of genomes recovered in a metagenomic survey belonging to 200 bacterial and archaeal families that were either previously undescribed or that exhibit an extremely rare distribution on the current earth. Such diversity is underpinned by the widespread occurrence of sulfite-, thiosulfate, tetrathionate-, and sulfur-reduction, and paucity of sulfate-reduction machineries in these taxa; hence greatly expanding lineages mediating reductive sulfur cycling processes in the tree of life. Analysis of the overlaying water community demonstrated that oxygen intrusion lead to the development of a significantly less diverse community dominated by well-characterized lineages and a prevalence of oxidative sulfur cycling processes. Such transition from ancient novelty to modern commonality underscores the profound impact of the great oxygenation event on the earths surficial anoxic community. It also suggests that novel and rare lineages encountered in current anaerobic habitats could represent taxa once thriving in an anoxic earth, but have failed to adapt to earths progressive oxygenation.

microbiology↗

bioRxiv2021

Modeling features of addiction with an oral oxycodone self-administration paradigm

Prescription opioid use is an initiating factor driving the current opioid epidemic. There are several challenges with modeling prescription opioid addiction. First, prescription opioids such as oxycodone are orally self-administered and have different pharmacokinetics and dynamics than morphine or fentanyl. This oral route of administration determines the pharmacokinetic profile, which is critical for establishing reliable drug-reinforcement associations in animals. Moreover, the pattern of intake and environment in which addictive drugs are self-administered intake are critical determinants of the levels of drug intake, sensitization and relapse behavior. This is an important consideration with prescription opioid use, which is characterized by continuous drug access in familiar environments. Thus, to model features of prescription opioid use and the transition to abuse, we present an oral oxycodone self-administration paradigm that is administered in the home cage. Mice voluntarily self-administer oxycodone in this paradigm without any taste modification such as sweeteners, and exhibit preference for oxycodone, escalation of intake, physical signs of dependence, reinstatement of seeking after withdrawal, and a subset of animals demonstrate drug taking that is resistant to aversive consequences. This model could be useful for studying the neurobiological substrates specifically relevant to prescription opioid abuse.

neuroscience↗

bioRxiv2020

Oleic acid protects Caenorhabditis mothers from mating-induced death

Reproduction comes at a cost, including death. Previous studies of the interconnections between reproduction, lifespan, and fat metabolism in C. elegans were predominantly performed in low-reproduction conditions. To understand how increased reproduction affects lifespan and fat metabolism, we examined mated worms; we find that a {Delta}9 desaturase, FAT-7, is significantly up-regulated. Dietary supplementation of oleic acid (OA), the immediate downstream product of FAT-7 activity, restores fat storage and completely rescues mating-induced death, while other fatty acids cannot. OA-mediated lifespan restoration is also observed in C. elegans mutants suffering increased death from short-term mating, and in mated C. remanei females, indicating a conserved role of oleic acid in post-mating lifespan regulation. Because OA supplementation does not further increase the reproductive span or the brood size of mated C. elegans mothers, our results suggest that altering specific fat metabolism uncouples reproduction and somatic lifespan regulation, providing potent targets to ameliorate the cost of reproduction.

genetics↗

bioRxiv2020

High throughput identification of miR-145 targets in human articular chondrocytes

ObjectiveMicroRNAs play a key role in biological processes, including cartilage development and homeostasis and are dysregulated in many diseases, including osteoarthritis. MiR-145 modulation induces profound changes in the human articular chondrocyte (HAC) phenotype, partially through direct repression of SOX9. Since miRNAs can simultaneously silence multiple targets, we aimed to identify the whole targetome of miR-145 in HACs. This information is critical if miR-145 is to be considered a target for cartilage repair. MethodsRIP-seq (RNA-immunoprecipitation plus HT-sequencing) of miRISC (miRNA-induced silencing complex) was performed in HACs overexpressing miR-145 to identify miR-145 direct targets. The motif discovery method cWords was used to assess enrichment on miR-145 seed matches in the identified targets. RT-qPCR, Western (immuno-)blot and luciferase assays were used to validate miRNA-target interactions. ResultsMiR-145 overexpression affects the expression of over 350 genes and directly targets more than 50 mRNAs through the 3UTR or, more commonly, the coding region. We also demonstrate that miR-145 targets DUSP6, involved in cartilage organization and development, at the translational level. DUSP6 depletion using specific siRNAs lead to MMP13 up-regulation, suggesting that miR-145-mediated DUSP6 depletion contributes to the effect of miR-145 on MMP13 expression. ConclusionWe demonstrate that miR-145 directly targets several genes in primary chondrocytes including those involved in the expression of the extracellular matrix and inflammation. Thus, we propose miR-145 as an important regulator of chondrocyte function and a new target for cartilage repair.

cell biology↗

bioRxiv2020

Lineage reversion drives WNT independence in intestinal cancer

The WNT pathway is a fundamental regulator of intestinal homeostasis and hyperactivation of WNT signaling is the major oncogenic driver in colorectal cancer (CRC). To date, there are no described mechanisms that bypass WNT dependence in intestinal tumors. Here, we show that while WNT suppression blocks tumor growth in most organoid and in vivo CRC models, the accumulation of CRC-associated genetic alterations enables drug resistance and WNT-independent growth. In intestinal epithelial cells harboring mutations in KRAS or BRAF, together with disruption of p53 and SMAD4, transient TGF{beta} exposure drives YAP/ TAZ-dependent transcriptional reprogramming and lineage reversion. Acquisition of embryonic intestinal identity is accompanied by a permanent loss of adult intestinal lineages, and long-term WNT-independent growth. This work delineates genetic and microenvironmental factors that drive WNT inhibitor resistance, identifies a new mechanism for WNT-independent CRC growth and reveals how integration of associated genetic alterations and extracellular signals can overcome lineage-dependent oncogenic programs.

cancer biology↗

bioRxiv2019

Reduction of insulin/IGF-1 receptor rejuvenates immunity via positive feedback circuit

Immunosenescence is considered an inevitable decline in immune function during aging. Here we show that genetic inhibition of the DAF-2/insulin/IGF-1 receptor drastically delays immunosenescence and rejuvenates immunity in C. elegans. We find that p38 mitogen-activated protein kinase 1 (PMK-1), a key determinant of immunosenescence, is dispensable for this rejuvenated immunity. Instead, we demonstrate that longevity-promoting DAF-16/FOXO and heat-shock transcription factor 1 (HSF-1) increase immunocompetence in old daf-2(-) animals. The upregulation of DAF-16/FOXO and HSF-1 decreases the expression of the zip-10/bZIP transcription factor, which in turn downregulates INS-7, an agonistic insulin-like peptide, resulting in further reduction of insulin/IGF-1 signaling (IIS). Thus, reduced IIS bypasses immunosenescence and rejuvenates immunity via the upregulation of anti-aging transcription factors that modulate an endocrine insulin-like peptide through a positive feedback mechanism. Because many functions of IIS are conserved across phyla, our study may lead to the development of strategies for human immune rejuvenation.

genetics↗

bioRxiv2019

Salient images: Evidence for a component process architecture for visual imagination.

The ability to visualise different people and places in imagination is a core element of human cognition. Contemporary neuroimaging research highlights regions of primary visual cortex as important in instantiating images in the minds eye. Here we combine task-based functional magnetic resonance imaging with measures of intrinsic brain organisation to show the ventral attention, or salience, network, also plays an important role in visual imagination. In a task-based study we replicated prior observations of regions of medial occipital cortex, including Brodmann Area 17, showing greater neural activity during imagination than when perceiving similar stimuli. In addition, we found regions of the ventral attention network, and in particular right dorsolateral prefrontal cortex (BA 9/46), were activated by the same acts of imagination. In a subsequent resting-state study, we demonstrated medial occipital cortex regions form a functional network with regions of the ventral attention network that were also active during imagination. Furthermore, this pattern was maximised in an overlapping region of right dorsolateral prefrontal cortex for individuals whose self-reported imagery had stronger negative affect. Together these data suggest visual imagination relies on functional interactions between regions of primary visual cortex with the ventral attention system, and in particular, with a region of right dorsolateral prefrontal cortex.

neuroscience↗

bioRxiv2019

De Novo Growth Of Methanogenic Granules Indicates A Biofilm Life-Cycle With Complex Ecology

Methanogenic sludge granules are densely packed, small (diameter, approx. 0.5-2.0 mm) spherical biofilms found in anaerobic digesters used to treat industrial wastewaters, where they underpin efficient organic waste conversion and biogas production. A single digester contains millions of individual granules, each of which is a highly-organised biofilm comprised of a complex consortium of likely billions of cells from across thousands of species - but not all granules are identical. Whilst each granule theoretically houses representative microorganisms from all of the trophic groups implicated in the successive and interdependent reactions of the anaerobic digestion process, parallel granules function side-by-side in digesters to provide a meta-organism of sorts. Granules from a full-scale bioreactor were size-separated into small, medium and large granules. Laboratory-scale bioreactors were operated using only small (0.6-1 mm), medium (1-1.4 mm) or large (1.4-1.8 mm) granules, or unfractionated (naturally distributed) sludge. After >50 days of operation, the granule size distribution in each of the small, medium and large bioreactor types had diversified beyond - to both bigger and smaller than - the size fraction used for inoculation. New granules were analysed by studying community structure based on high-throughput 16S rRNA gene sequencing. Methanobacterium, Aminobacterium, Propionibacteriaceae and Desulfovibrio represented the majority of the community in new granules. H2-using, and not acetoclastic, methanogens appeared more important, and were associated with abundant syntrophic bacteria. Multivariate integration analyses identified distinct discriminant taxa responsible for shaping the microbial communities in different-sized granules, and along with alpha diversity data, indicated a possible biofilm life cycle.\n\nImportanceMethanogenic granules are spherical biofilms found in the built environment, where despite their importance for anaerobic digestion of wastewater in bioreactors, little is understood about the fate of granules across their entire life. Information on exactly how, and at what rates, methanogenic granules develop will be important for more precise and innovative management of environmental biotechnologies. Microbial aggregates also spark interest as subjects in which to study fundamental concepts from microbial ecology, including immigration and species sorting affecting the assembly of microbial communities. This experiment is the first, of which we are aware, to compartmentalise methanogenic granules into discrete, size-resolved fractions, which were then used to separately start up bioreactors to investigate the granule life cycle. The evidence, and extent, of de novo granule growth, and the identification of key microorganisms shaping new granules at different life-cycle stages, is important for environmental engineering and microbial ecology.

microbiology↗

bioRxiv2019

Hello, is that me you are looking for? A re-examination of the role of the DMN in off-task thought

Neural activity within the default mode network (DMN) is widely assumed to relate to processing during off-task states, however it remains unclear whether this association emerges from a shared role in self or social cognition. In the current study, we examine the possibility that the role of the DMN in ongoing thought emerges from contributions to specific features of off-task experience such as self-relevant or social content. A group of participants described their experiences while performing a laboratory task over a period of days. In a different session, neural activity was measured while participants performed self/other judgements. Despite the prominence of social and personal content in off-task reports, there was no association with neural activity during off-task trait adjective judgements. Instead, during both self and other judgements we found recruitment of caudal posterior cingulate cortex - a core DMN hub - was above baseline for individuals whose laboratory experiences were characterised as detailed. These data provide little support for a role of the DMN in self or other content in the off-task state and instead suggest a role in how on-going thought is represented.

neuroscience↗

bioRxiv2018

Horizontal gene transfer as an indispensible driver for Neocallimastigomycota evolution into a distinct gut-dwelling fungal lineage

Survival and growth of the anaerobic gut fungi (AGF, Neocallimastigomycota) in the herbivorous gut necessitate the possession of multiple abilities absent in other fungal lineages. We hypothesized that horizontal gene transfer (HGT) was instrumental in forging the evolution of AGF into a phylogenetically distinct gut-dwelling fungal lineage. Patterns of HGT were evaluated in the transcriptomes of 27 AGF strains, 22 of which were isolated and sequenced in this study, and 4 AGF genomes broadly covering the breadth of AGF diversity. We identified 283 distinct incidents of HGT in AGF transcriptomes, with subsequent gene duplication resulting in an HGT frequency of 2.1-3.6% in AGF genomes. The majority of HGT events were AGF specific (91.5%) and wide (70.7%), indicating their occurrence at early stages of AGF evolution. The acquired genes allowed AGF to expand their substrate utilization range, provided new venues for electron disposal, augmented their biosynthetic capabilities, and facilitated their adaptation to anaerobiosis. The majority of donors were anaerobic fermentative bacteria prevalent in the herbivorous gut. This work strongly indicates that HGT indispensably forged the evolution of AGF as a distinct fungal phylum and provides a unique example of the role of HGT in shaping the evolution of a high rank taxonomic eukaryotic lineage. ImportanceThe anaerobic gut fungi (AGF) represent a distinct basal phylum lineage (Neocallimastigomycota) commonly encountered in the rumen and alimentary tracts of herbivores. Survival and growth of anaerobic gut fungi in these anaerobic, eutrophic, and prokaryotes dominated habitats necessitates the acquisition of several traits absent in other fungal lineages. This manuscript assesses the role of horizontal gene transfer as a relatively fast mechanism for trait acquisition by the Neocallimastigomycota post sequestration in the herbivorous gut. Analysis of twenty-seven transcriptomes that represent the broad Neocallimastigomycota diversity identified 283 distinct HGT events, with subsequent gene duplication resulting in an HGT frequency of 2.1-3.6% in AGF genomes. These HGT events have allowed AGF to survive in the herbivorous gut by expanding their substrate utilization range, augmenting their biosynthetic pathway, providing new routes for electron disposal by expanding fermentative capacities, and facilitating their adaptation to anaerobiosis. HGT in the AGF is also shown to be mainly a cross-kingdom affair, with the majority of donors belonging to the bacteria. This work represents a unique example of the role of HGT in shaping the evolution of a high rank taxonomic eukaryotic lineage.

microbiology↗

bioRxiv2018

Legionella pneumophila translocated translation inhibitors are required for bacterial-induced host cell cycle arrest

The cell cycle machinery controls diverse cellular pathways and is tightly regulated. Misregulation of cell division plays a central role in the pathogenesis of many disease processes. Various microbial pathogens interfere with the cell cycle machinery to promote host cell colonization. Although cell cycle modulation is a common theme among pathogens, the role that this interference plays in promoting diseases is unclear. Previously we demonstrated that the G1 and G2/M phases of the host cell cycle are permissive for Legionella pneumophila replication, while S phase provides a toxic environment for bacterial replication. In this study we show that L. pneumophila avoids host S phase by blocking host DNA synthesis and preventing cell cycle progression into S phase. Cell cycle arrest upon Legionella contact is dependent on the Icm/Dot secretion system. In particular, we found that cell cycle arrest is dependent on the intact enzymatic activity of translocated substrates that inhibits host translation. Moreover, we show that early in infection, the presence of these translation inhibitors is crucial to induce the degradation of the master regulator cyclin D1. Our results demonstrate that the bacterial effectors that inhibit translation are associated with preventing entry of host cells into a phase associated with restriction of L. pneumophila. Furthermore, control of cyclin D1 may be a common strategy used by intracellular pathogens to manipulate the host cell cycle and promote bacterial replication.\n\nSignificanceRecently, we showed that host cell cycle regulatory proteins control L. pneumophila growth. In particular, bacterial replication was found to be depressed in S-phase. This indicates that bacterial control of the host cell cycle can limit exposure of the pathogen to antimicrobial events that are cycle-specific. Here we uncovered bacterial factors that induce host cell cycle arrest by inhibiting host protein synthesis and preventing S phase transition. These data are consistent with S-phase toxicity serving as an important antimicrobial response that limits growth of some intracellular pathogens. Moreover, identification of microbial factors that block cell cycle progression and uncovering host cell cycle partners are candidates for future drug development. Our data point to a unifying role of the cell cycle in multiple disease processes.

microbiology↗

bioRxiv2018

Phenogenon: Gene to Phenotype Associations for Rare Genetic Diseases

As genome sequencing is increasingly applied to molecular diagnosis of rare Mendelian disorders, large number of patients with diverse phenotypes have their genomic and phenotypic data pooled together to uncover new genotype - phenotype relations. We introduce Phenogenon, a method that combines: the power of Human Phenotype Ontology for describing patient phenotypes, gnomAD for estimating rare variant population frequency, and CADD for variant pathogenicity prediction. By using a divide and conquer approach, we demonstrate here that Phenogenon is able to uncover true gene to phenotype relations, such as \"ABCA4 - Macular dystrophy\" and \"SCN1A - Seizures\". Additionally, it accurately infers mode of inheritance, such as a recessive mode of inheritance in the case of the \"ABCA4 - Macular dystrophy\" relationship and a dominant mode of inheritance with the \"SCN1A - Seizures\" relationship. We also found that CADD has more power to detect early-onset rare genetic diseases than late-onset diseases. In this study, we ran Phenogenon against a diverse cohort of 3288 patients. Among the top 13 gene-phenotype relations, seven were previously known. We also highlight four potentially novel gene - phenotype relations such as \"SIPA1L3 - Abnormal electroretinogram\".

bioinformatics↗

bioRxiv2017

Scaffolding imagination: A role for medial frontal cortex in the expression of off-task thought

We often think about people, places and events that are outside of our immediate environment. Although prior studies have explored how we can reduce the occurrence of these experiences, the neurocognitive process through which they are produced are less understood. The current study builds on developmental and evolutionary evidence that language helps organise and express our thoughts. Behaviorally, we found the occurrence of task unrelated thought (TUT) in easy situations was associated with thinking in words. Using experience sampling data, in combination with online measures of neural function, we established that activity in a region of anterior cingulate cortex / medial-prefrontal cortex (mPFC) tracked with changes in the expression of TUT. This region is at the intersection of two mPFC clusters identified through their association with variation in aspects of spontaneous thought: thinking in words (dorsal) and mental time travel (ventral). Finally, using meta-analytic decoding we confirmed the dorsal/ventral distinction within mPFC corresponding to a functional difference between domains linked to language and meaning and those linked to memory and scene construction. This evidence suggests a role for mPFC in the expression of TUT that may emerge from interactions with distributed neural signals reflecting processes such as language and memory.

animal behavior and cognition↗

bioRxiv2017

Isolated from input: Transmodal cortex in the default mode network supports perceptually-decoupled and conceptually-guided cognition

The default mode network supports a variety of mental operations such as semantic processing, episodic memory retrieval, mental time travel and mind-wandering, yet the commonalities between these functions remains unclear. One possibility is that this system supports cognition that is independent of the immediate environment; alternatively or additionally, it might support higher-order conceptual representations that draw together multiple features. We tested these accounts using a novel paradigm that separately manipulated the availability of perceptual information to guide decision-making and the representational complexity of this information. Using task based imaging we established regions that respond when cognition combines both stimulus independence with multi-modal information. These included left and right angular gyri and the left middle temporal gyrus. Although these sites were within the default mode network, they showed a stronger response to demanding memory judgements than to an easier perceptual task, contrary to the view that they support automatic aspects of cognition. In a subsequent analysis, we showed that these regions were located at the extreme end of a macroscale gradient, which describes gradual transitions from sensorimotor to transmodal cortex. This shift in the focus of neural activity towards transmodal, default mode, regions might reflect a process of isolation from specific sensory inputs that enables conceptually rich cognitive states to be generated in the absence of input.\n\nHighlights O_LIBrain regions supporting meaning overlap with stimulus independence.\nC_LIO_LIBilateral angular gyri and left MTG respond strongly to both features of cognition.\nC_LIO_LIThese patterns reflect a shift in activity towards regions of transmodal cortex.\nC_LIO_LIComplex memory representations may emerge in cortical areas distant from input.\nC_LI

neuroscience↗

bioRxiv2016

Phenopolis: an open platform for harmonization and analysis of sequencing and phenotype data

SummaryPhenopolis is an open-source web server which provides an intuitive interface to genetic and phenotypic databases. It integrates analysis tools which include variant filtering and gene prioritisation based on phenotype. The Phenopolis platform will accelerate clinical diagnosis, gene discovery and encourage wider adoption of the Human Phenotype Ontology in the study of rare disease.\n\nAvailability and ImplementationA demo of the website is available at http://phenopolis.github.io (username: demo, password: demo123). If you wish to install a local copy, souce code and installation instruction are available at https://github.com/pontikos/phenopolis. The software is implemented using Python, MongoDB, HTML/Javascript and various bash shell scripts.\n\nContactn.pontikos@ucl.ac.uk\n\nSupplementary informationhttp://phenopolis.github.io

bioinformatics↗

bioRxiv2016

AGFusion: annotate and visualize gene fusions

SummaryThe discovery of novel gene fusions in tumor samples has rapidly accelerated with the rise of next-generation sequencing. A growing number of tools enable discovery of gene fusions from RNA-seq data. However it is likely that not all gene fusions are driving tumors. Assessing the potential functional consequences of a fusion is critical to understand their driver role. It is also challenging as gene fusions are described by chromosomal breakpoint coordinates that need to be translated into an actual amino acid fusion sequence and predicted domain architecture of the fusion proteins. Currently there are no easy-to-use tools that can automatically reconstruct and visualize fusion proteins from genomic breakpoints. To facilitate the functional interpretation of gene fusions, we developed AGFusion, available as an online web tool that can be readily used by non-computational researchers as well as a python package that can be built into computational pipelines. With minimal input from the user, AGFusion predicts the cDNA, CDS, and protein sequences of all gene fusion products based on all combinations of gene isoforms. For protein coding fusions, AGFusion can annotate and visualize the protein domain architecture. AGFusion currently supports Homo sapiens (genome builds GRCh37 and GRCh38) and Mus musculus (genome build GRCm38) and new genomes can easily be added.\n\nAvailabilityAGFusion python package is freely available at https://github.com/murphycj/AGFusion under the MIT license. The AGFusion web app is available at http://agfusion.info

bioinformatics↗