Best practice data life cycle approaches for the life sciences
- Griffin, Philippa, Khadake, Jyoti, LeMay, Kate, Lewis, Suzanna, Orchard, Sandra, Pask, Andrew, Pope, Bernard, Roessner, Ute, Russell, Keith, Seemann, Torsten, Treloar, Andrew, Tyagi, Sonika, Christiansen, Jeffrey, Dayalan, Saravanan, Gladman, Simon, Hangartner, Sandra, Hayden, Helen, Ho, William, Keeble-Gagnère, Gabriel, Korhonen, Pasi, Neish, Peter, Prestes, Priscilla, Richardson, Mark, Watson-Haigh, Nathan, Wyres, Kelly, Young, Neil, Schneider, Maria
- Authors: Griffin, Philippa , Khadake, Jyoti , LeMay, Kate , Lewis, Suzanna , Orchard, Sandra , Pask, Andrew , Pope, Bernard , Roessner, Ute , Russell, Keith , Seemann, Torsten , Treloar, Andrew , Tyagi, Sonika , Christiansen, Jeffrey , Dayalan, Saravanan , Gladman, Simon , Hangartner, Sandra , Hayden, Helen , Ho, William , Keeble-Gagnère, Gabriel , Korhonen, Pasi , Neish, Peter , Prestes, Priscilla , Richardson, Mark , Watson-Haigh, Nathan , Wyres, Kelly , Young, Neil , Schneider, Maria
- Date: 2018
- Type: Text , Journal article
- Relation: F1000 Research Vol. 6, no. (2018), p. 1-28
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- Description: Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a 'life cycle' view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain. Here we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on 'omics' datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices. © 2018 Griffin PC et al.
- Authors: Griffin, Philippa , Khadake, Jyoti , LeMay, Kate , Lewis, Suzanna , Orchard, Sandra , Pask, Andrew , Pope, Bernard , Roessner, Ute , Russell, Keith , Seemann, Torsten , Treloar, Andrew , Tyagi, Sonika , Christiansen, Jeffrey , Dayalan, Saravanan , Gladman, Simon , Hangartner, Sandra , Hayden, Helen , Ho, William , Keeble-Gagnère, Gabriel , Korhonen, Pasi , Neish, Peter , Prestes, Priscilla , Richardson, Mark , Watson-Haigh, Nathan , Wyres, Kelly , Young, Neil , Schneider, Maria
- Date: 2018
- Type: Text , Journal article
- Relation: F1000 Research Vol. 6, no. (2018), p. 1-28
- Full Text:
- Reviewed:
- Description: Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a 'life cycle' view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain. Here we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on 'omics' datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices. © 2018 Griffin PC et al.
Deguelin exerts potent nematocidal activity via the mitochondrial respiratory chain
- Preston, Sarah, Korhonen, Pasi, Mouchiroud, Laurent, Cornaglia, Matteo, McGee, Sean, Young, Neil, Davis, Rohan, Crawford, Simon, Nowell, Cameron, Ansell, Brendan, Fisher, Gillian, Andrews, Katherine, Chang, Bill, Gijs, Martin, Sternberg, Paul, Auwerx, Johan, Baell, Jonathan, Hofmann, Andreas, Jabbar, Abdul, Gasser, Robin
- Authors: Preston, Sarah , Korhonen, Pasi , Mouchiroud, Laurent , Cornaglia, Matteo , McGee, Sean , Young, Neil , Davis, Rohan , Crawford, Simon , Nowell, Cameron , Ansell, Brendan , Fisher, Gillian , Andrews, Katherine , Chang, Bill , Gijs, Martin , Sternberg, Paul , Auwerx, Johan , Baell, Jonathan , Hofmann, Andreas , Jabbar, Abdul , Gasser, Robin
- Date: 2017
- Type: Text , Journal article
- Relation: FASEB Journal Vol. 31, no. 10 (2017), p. 4515-4532
- Full Text: false
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- Description: As a result of limited classes of anthelmintics and an over-reliance on chemical control, there is a great need to discover new compounds to combat drug resistance in parasitic nematodes. Here, we show that deguelin, a plant-derived rotenoid, selectively and potently inhibits the motility and development of nematodes, which supports its potential as a lead candidate for drug development. Furthermore, we demonstrate that deguelin treatment significantly increases gene transcription that is associated with energy metabolism, particularly oxidative phosphorylation and mitoribosomal protein production before inhibiting motility. Mitochondrial tracking confirmed enhanced oxidative phosphorylation. In accordance, real-time measurements of oxidative phosphorylation in response to deguelin treatment demonstrated an immediate decrease in oxygen consumption in both parasitic (Haemonchus contortus) and free-living (Caenorhabditis elegans) nematodes. Consequently, we hypothesize that deguelin is exerting its toxic effect on nematodes as a modulator of oxidative phosphorylation. This study highlights the dynamic biologic response of multicellular organisms to deguelin perturbation. © FASEB.
Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation
- Li, Facai, Lok, James, Gasser, Robin, Korhonen, Pasi, Sandeman, Mark, Shi, Deshi, Zhou, Rui, Li, Xiangrui, Zhou, Yanqin, Zhao, Junlong, Hu, Min
- Authors: Li, Facai , Lok, James , Gasser, Robin , Korhonen, Pasi , Sandeman, Mark , Shi, Deshi , Zhou, Rui , Li, Xiangrui , Zhou, Yanqin , Zhao, Junlong , Hu, Min
- Date: 2014
- Type: Text , Journal article
- Relation: International Journal for Parasitology Vol. 44, no. 7 (2014), p. 485-496
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- Description: Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf-2/. Hc-DAF-2 in the biology and development of H. contortus, particularly in the transition to parasitism. © 2014 Australian Society for Parasitology Inc.
- Authors: Li, Facai , Lok, James , Gasser, Robin , Korhonen, Pasi , Sandeman, Mark , Shi, Deshi , Zhou, Rui , Li, Xiangrui , Zhou, Yanqin , Zhao, Junlong , Hu, Min
- Date: 2014
- Type: Text , Journal article
- Relation: International Journal for Parasitology Vol. 44, no. 7 (2014), p. 485-496
- Full Text:
- Reviewed:
- Description: Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf-2/. Hc-DAF-2 in the biology and development of H. contortus, particularly in the transition to parasitism. © 2014 Australian Society for Parasitology Inc.
Low cost whole-organism screening of compounds for anthelmintic activity
- Preston, Sarah, Jabbar, Abdul, Nowell, Cameron, Joachim, Anja, Ruttkowski, Barbel, Baell, Jonathan, Cardno, Tony, Korhonen, Pasi, Piedrafita, David, Ansell, Brendan, Jex, Aaron, Hofmann, Andreas, Gasser, Robin
- Authors: Preston, Sarah , Jabbar, Abdul , Nowell, Cameron , Joachim, Anja , Ruttkowski, Barbel , Baell, Jonathan , Cardno, Tony , Korhonen, Pasi , Piedrafita, David , Ansell, Brendan , Jex, Aaron , Hofmann, Andreas , Gasser, Robin
- Date: 2015
- Type: Text , Journal article
- Relation: International Journal for Parasitology Vol. 45, no. 5 (2015), p. 333-343
- Full Text: false
- Reviewed:
- Description: Due to major problems with drug resistance in parasitic nematodes of animals, there is a substantial need and excellent opportunities to develop new anthelmintics via genomic-guided and/or repurposing approaches. In the present study, we established a practical and cost-effective whole-organism assay for the in vitro-screening of compounds for activity against parasitic stages of the nematode Haemonchus contortus (barber's pole worm). The assay is based on the use of exsheathed L3 (xL3) and L4 stages of H. contortus of small ruminants (sheep and goats). Using this assay, we screened a panel of 522 well-curated kinase inhibitors (GlaxoSmithKline, USA; code: PKIS2) for activity against H. contortus by measuring the inhibition of larval motility using an automated image analysis system. We identified two chemicals within the compound classes biphenyl amides and pyrazolo[1,5-α]pyridines, which reproducibly inhibit both xL3 and L4 motility and development, with IC50s of 14-47μM. Given that these inhibitors were designed as anti-inflammatory drugs for use in humans and fit the Lipinski rule-of-five (including bioavailability), they show promise for hit-to-lead optimisation and repurposing for use against parasitic nematodes. The screening assay established here has significant advantages over conventional methods, particularly in terms of ease of use, throughput, time and cost. Although not yet fully automated, the current assay is readily suited to the screening of hundreds to thousands of compounds for subsequent hit-to-lead optimisation. The current assay is highly adaptable to many parasites of socioeconomic importance, including those causing neglected tropical diseases. This aspect is of major relevance, given the urgent need to deliver the goals of the London Declaration (
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