MetaboNews Masthead
Published in partnership between
TMIC and the Metabolomics Society
Issue 43 - March 2015

CONTENTS:


Online version of this newsletter:
 http://www.metabonews.ca/Mar2015/MetaboNews_Mar2015.htm

Welcome to the forty-third issue of MetaboNews, a monthly newsletter published in partnership between The Metabolomics Innovation Centre (TMIC, http://www.metabolomicscentre.ca/) and the international Metabolomics Society (http://www.metabolomicssociety.org/), to keep metabolomics researchers and other professionals informed about new technologies, software, databases, events, job postings, conferences, training opportunities, interviews, publications, awards, and other newsworthy items concerning metabolomics. MetaboNews represents the one-stop-shop for the very latest and most critical news about the science of metabolomics. In this issue, we feature a Metabolomics Spotlight article on the detection of drug hepatotoxicity in rats, and a metabolomics interview with Paige Lacy of the University of Alberta.
This issue of MetaboNews is supported by:

Metanomics Health
    
Chenomx -- Metabolite Discovery & Measurement    
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Metanomics Health GmbH
Chenomx Inc.
mzCloud Mass Spectral Database

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Metabolomics Society News

CONFERENCE CORNER

11th Annual International Conference of the Metabolomics Society
Location: San Francisco, USA
Date: June 29 - July 2, 2015
Website: http://metabolomics2015.org/
Registrations and abstract submissions are now open for the premier metabolomics conference of 2015.
Abstract submissions close 15th March.
The Metabolomics Society will provide 20 travel awards to assist young members to attend the conference. 10 awards are available to student members of the Society and 10 new awards are available to early-career members within 5 years of their highest degree (i.e., post-docs). Winners will be selected based on the abstracts, and you need to be a member of the Metabolomics Society at least 3 months prior to the conference to be eligible. Sign up or renew now to avoid disappointment!
http://metabolomicssociety.org/members-center/membership

2017 Metabolomics Society Conference in Greater Asia region
The Metabolomics Society is calling for interested members in the Greater Asia region (incorporating Asia and Australasia) to express their interest in hosting the 2017 annual Metabolomics Society meeting (http://metabolomics2017.org). Please send notice of your interest using this form by 15th March 2015. You should name individuals who will be key to forming a Local Organizing Committee (LOC), and suggest potential cities and venues in which the conference could be held. The LOC will report to the Metabolomics Society and assist A-S-K staff to organize the conference. The tasks of the LOC are to ensure national and regional support for the conference, to assist the Society in administrative planning and, most importantly, to chair and organize the scientific management of the conference, including forming an International Organizing Committee that has the responsibility for scientific aspects of the meeting. Please complete the application form outlining your ideas to maximize the scientific quality and outreach of the conference. For further enquiries please contact the Society via A-S-K Associates (metabolomics@askusa.com).

Support for non-Society conferences and workshops
The Metabolomics Society provides small grants to support events that promote metabolomics. The funding may be used to provide student prizes, travel awards or catering for small events such as symposia, workshops, seminars and short-courses. The Society may also sponsor larger conferences where there is strategic opportunity to promote metabolomics science within other scientific disciplines.
In 2015 the Metabolomics Society will support:
 For more information, or to apply for funding for your event, see: http://metabolomicssociety.org/index.php/events/event-funding Society Support for Early-career Scientist at the Third PANIC meeting in San Diego, CASociety Support for Early-career Scientist Yevgeniy Izrayelit
The Metabolomics Society supported one award to support student or early career travel for the third annual Practical Applications of NMR in Industry Conference (PANIC) meeting in San Diego, California. Dr. Yevgeniy Izrayelit, Postdoctoral Fellow at Brown University by the PANIC scientific committee to receive the award and present an oral talk on “2D NMR-Based Metabolomics Uncovers Interactions between Conserved Biochemical Pathways in the Model Organism Caenorhabditis elegans”. Yevgeniy was very grateful to the Metabolomics Society for the award because he “had an amazing experience at PANIC and would not have been able to travel to the meeting without the Society’s support.” (Photo caption: Yevgeniy Izrayelit (Awardee, L) and Dan Bearden (Treasurer, R) at the PANIC Meeting)


MEMBERS CORNER

 Early-career Members Network (EMN)
The EMN is dedicated to and run by early-career scientists who are members of the Metabolomics Society and are from academia, government, or industry. The network aims to provide a forum for metabolomics researchers at the start of their professional career.

11th Annual International Conference of the Metabolomics Society
The EMN will host four workshop sessions tailored for the needs of the early-career members. To attend the conference and workshops, you can apply for the Early-Career Travel Awards. More details to follow soon!

EMN webinar series
The EMN is planning to establish a series of online webinars from 2015 onwards.
Save the date on your calendar for our second session of the EMN webinar series: coming to you live on Thursday March 5th 2015 (11:00am CST, 9:00am PST, 12:00pm EST, 5:00pm GMT). Session 2 of the EMN webinar series will feature our expert speaker Dr. Lloyd Sumner, who will provide a cutting edge 20 minute presentation (please see the event flyer). The presentation will introduce novel software entitled Plant Metabolite Annotation Toolbox (PlantMAT) and a sophisticated UHPLC-MS-SPE- NMR instrumental ensemble that are being used for ‘sequencing’ the first plant metabolomes of the model plant systems Arabidopsis and Medicago truncatula. There will be an opportunity to pose key questions to Dr. Lloyd Sumner at the end of the session. Please, register using the following link: https://attendee.gotowebinar.com/register/259087085732346370

Please note that the second webinar is freely available for everyone courtesy of the Metabolomics Society and will be uploaded to the society's website. All subsequent sessions from our series will be available for members of the Metabolomics Society only with the opportunity to revisit live recorded sessions at your own convenience. Make sure to check the Metabolomics Society website, Twitter, Facebook for updates on the webinar.

Please feel free to contact us via info.emn@metabolomicssociety.org if you have any suggestions or comments regarding our planned activities this year (i.e., online webinars and workshops). If you think you have a great idea for a new activity we should organise then please do share with us; the EMN can only be a success with your support and ideas!!

Metabolomics Society Video Content Is Now Available!
The Society is pleased to announce a new service for the metabolomics community. Exciting video content is available immediately, for free. Coming soon, we will have exclusive Members Only content, so update your membership soon! We currently have two exciting features for general access:
EMN Webinar with Oscar Yanes
In case you missed the live webinar of Dr. Oscar Yanes (29 January 2015), hosted by the Early-career Members Network on behalf of the Metabolomics Society, you can now watch the recording on-line! The full webinar is available for free, including the Q/A session at the end of the presentation. Watch it soon!

This was the inaugural EMN-sponsored webinar, and the overall satisfaction score, in response to our online survey, was very positive with an average of 4 out of 5. So thank you to those who took part! We are always looking for ways to improve so if you have any ideas or would like to suggest a future topic for a webinar then please don’t hesitate to contact us using the following e-mail: info.emn@metabolomicssociety.org

Metabolomics2014 Workshops
The video recordings of all the workshops presented at the Metabolomics Society Annual International Meeting in Tsuroka, Japan are now available for free. Soon, as a Members-Only benefit, the keynote and plenary lectures from Metabolomics2014 will be posted. Please check the Resources/Video tab on the Society website often to stay up to date!
Membership News for 2015
For those of you who have not yet renewed your membership of the Metabolomics Society for 2015, the early bird discount has now ended. However, renewing your membership still allows you to claim a special members only price at Metabolomics 2015 as well as a host of other membership benefits which are listed here. To join the society or to renew your membership, go to http://metabolomicssociety.org/members-center/membership. For any questions regarding membership, please contact the Membership Secretary Jennifer Kirwan at membershipsec@metabolomicssociety.org.


TASK GROUPS CORNER

Metabolite Identification Task Group
CASMI-2014 has closed and we received six submissions from across the globe. Many thanks to all who submitted and for the positive comments. The solutions will be available soon as will the winner(s)! See http://www.casmi-contest.org/2014/index.shtml

Data Quality Task Group
The Data Quality Task Group (DQTG) is developing a short survey to assess current analytical quality control practices within the metabolomics community. This survey will help the DQTG in planning what approaches to take for future activities of the Task Group. Watch the Metabolomics Society website and information feeds for upcoming news about the survey.


INTERNATIONAL AFFILIATES CORNER

Australian & New Zealand Metabolomics Network (ANZMN)
Visit https://sites.google.com/site/anzmn2/
Members of the ANZMN, including Dr. Darren Creek and Dr. Camilla Hill, will give talks on their latest research at the Systems Biology Institute Workshop at 11:00am on Tuesday 3rd March in the level five seminar room at the Kenneth Myer Building, 30 Royal Parade, Parkville, University of Melbourne with networking and light lunch from 12:30pm). This is a great chance to hear from some of the top metabolomics researchers in Australia. You can find out more about the event at https://www.dropbox.com/s/zikypn0sqgd4hsd/Systems%20Metabolomics%20March2015.pdf?dl=0 and at http://sbiaustralia.org/outreach/vicprogram/, and you can register via https://www.eventbrite.com.au/e/systems-metabolomics-a-research-collaborative-tickets-15739363861 if you wish to attend.

The Garvan Institute of Medical Research in Sydney will be hosting the 1st Australian Cancer and, Metabolism Meeting on the 29th April to the 1st May. This will discuss the latest developments in metabolic regulation in cancer. You can see the event flyer here and the event website is at http://www.garvan.org.au/symposium/acmm if you are keen to go.

Korea Metabolomics Society (KoMetS)
Visit http://komets.or.kr/english05.html

2015 Annual Symposium of Korea Metabolomics Society
The 2015 annual symposium and general meeting has been scheduled. With the tile of “Metabolomics from the convergence of chemistry and biology”, the symposium will be held in Pusan from 2015 Annual Symposium of Korea Metabolomics SocietyApr. 2nd to 3rd. The program consists of 7 sessions, Drug discovery & pharmacology, Food & nutrition, Microbial metabolomics, Human diseases, Environment & Ecology, and Plant metabolomics. Prof. Christoph Wittmann (Saaland Univ., Germany), and Prof. Kauki Saito (RIKEN, Japan) will give plenary lecture. Prof. Yong-Su Jin (Univ. of Illinois, Urbana Champaign, USA) and Prof. Kiroaki Kodama (Chiba Univ., Japan) will be invited as keynote lecturers.


PUBLICATIONS CORNER

 Metabolomics journal, Vol. 11, Issue 1, February 2015
See the latest issue of our journal at: http://link.springer.com/journal/11306/11/1/page/1

In addition to the many excellent research papers, this issue contains the following contributions on the Metabolomics Society pages:
 Stay abreast of the latest metabolomics news via the Twitter feed on the front page of the website. Also you can follow us on Twitter: Metabolomics Society @MetabolomicsSoc and Metabolomics journal @Metabolomics. And you can visit us on Facebook.

 
 Software Spotlight

Metabolomics Spotlight

Metabolomics in vivo – detection of hepatotoxicity of drugs in rat studies
Feature article contributed by Dr. Hennicke Kamp, Group Leader, Experimental Toxicology and Ecology, BASF SE, Ludwigshafen, Germany

Introduction

Here, we briefly describe the results of our metabolomics investigations related to hepatotoxic compounds by applying MetaMap®Tox (a database of rat plasma metabolite profiles developed by metanomics GmbH and BASF SE), published in November 2014 in Toxicology Letters: “Detection of Hepatotoxicity Potential with Metabolite Profiling (metabolomics) of Rat Plasma” by W. Mattes, K. Davis, E. Fabian, J. Greenhaw, M. Herold , R. Looser, W. Mellert, S. Groeters, H. Marxfeld, N. Moeller, G. Montoya-Parra, A. Prokoudine, B. van Ravenzwaay, V. Strauss, T. Walk and H. Kamp (Toxicology Letters 230 (2014) 467-478).

The goal of safety evaluation studies is to characterize the hazards, such as organ toxicity posed by novel chemicals. A form of organ toxicity that is of significant importance for drug development is hepatotoxicity (Corsini et al., 2012; Horner et al., 2013). Although conventional parameters used to detect hepatotoxicity in drug safety assessment studies are generally informative, a significant need for improved parameters for early detection of hepatotoxicity exists. Previous work has shown that metabolomics can be used to detect different forms of organ toxicity in rats (Beger et al., 2010; van Ravenzwaay et al., 2012), specifically hepatotoxicity (Mattes et al., 2013). The studies reported here extended this observation to the question if such signals could also be detected in rats treated with compounds that can elicit hepatotoxicity in humans (i.e., drug-induced liver injury, DILI) but have not been reported to do so in rats. Nine compounds were selected on the basis of their known DILI potential, with six other compounds chosen as negative for DILI potential (see Table 1).

Compounds Used, Dose Levels, and Routes of Administration

Table 1. Compounds Used, Dose Levels, and Routes of Administration
Legend: p.o. – oral administration by gavage, ip – intraperitoneal injection, sc – subcutaneous injection, Diet – administration in feed

Methods

The conduct of experiments is described in detail in Mattes et al., 2014. Briefly, Wistar rats (CrI:WI(Han)) were dosed over a period of 28 days with the selected compounds as described in Table 1. At the end of the study, the animals were sacrificed by decapitation under isoflurane anesthesia. For all compounds, clinical pathology (hematology and clinical chemistry) was performed. For 12 compounds (phenytoin, captopril, nefazodone, nevirapine, valproic acid, zidovudine, atropine, lamivudine, mannitol, neomycin, streptomycin, or vancomycin), the liver was collected at necropsy and fixed in 10% neutral buffered formalin. Thereafter, liver tissues were processed to hematoxylin and eosin stained glass slides as described previously (Kamp et al., 2012) and examined by light microscopy.

K-EDTA samples were taken from the retro-orbital sinus in all rats under isoflurane anesthesia on study days 7, 14, and 28 for metabolite profiling analysis and extracted by a proprietary method. Two types of mass spectrometry-based metabolite profiling analysis were applied to all samples: GC-MS (gas chromatography-mass spectrometry) and LC-MS/MS (liquid chromatography-MS/MS) were used for broad profiling and hormone measurements as described in van Ravenzwaay et al. (Kamp et al., 2012, van Ravenzwaay et al., 2007). MetaMap®Tox is a unique database of biochemical profiles from rat plasma and comprehensive pharmacological and toxicological data based on more than 500 pharmaceuticals, chemicals, and agrochemicals after 7, 14, and 28 days of test substance treatment. Discriminating metabolite patterns for various toxicological modes of action (MoAs) were developed from the metabolite profiles in the MetaMap®Tox database (van Ravenzwaay et al., 2012). The comparison of the metabolome of a new compound against these patterns is a two-step process. Firstly, an algorithm used in the database yields a ranking list based on similarity of the test compound metabolic profile compared to specific patterns in MetaMap®Tox, using a median r value metric. Secondly, the metabolite changes are evaluated by an expert panel of experienced toxicologists to determine what may be described as “confirmed” matches.

Results and Discussion

Mild or modest changes in food consumption, body weight, clinical chemistry, and/or hematological parameters were seen in all studies. Parameters suggestive of liver injury were unchanged in most of these studies; serum ALT levels were very slightly, albeit statistically significantly, increased (1.2 to 1.3 fold) for atropine and mannitol, while total bilirubin was slightly increased (1.2 to 1.4 fold) for valproic acid, zidovudine, atropine, and mannitol. For phenytoin, minimal to slight centrilobular hepatocellular hypertrophy was observed. There were no microscopic findings in the hepatic parenchyma for any of the other compounds.

When compared against MetaMap®Tox, compounds clearly associated with human DILI generally resulted in plasma metabolite profiles that matched metabolite patterns associated with mechanisms of hepatotoxicity. By contrast, treatment of rats with compounds not associated with human DILI generally resulted in plasma metabolite profiles that, when queried against MetaMap®Tox, did not match metabolite patterns associated with mechanisms of hepatotoxicity. In this study, 8 of 9 DILI-positive compounds and 5 of 6 DILI-negative compounds were correctly identified as such (Figure 1), giving an overall sensitivity and specificity of 89% and 83%, respectively (albeit the total number of compounds examined is rather small).
Compounds with clear literature evidence of clinical DILI  
Compounds lacking clear literature evidence of clinical DILI

Figure 1. Liver-Related Toxicity MoA Pattern Matches per Compound
Legend: Summary counts of common patterns of liver toxicity for each compound treatment. High dose treatments were evaluated, except for those of captopril, where the low dose treatment was evaluated. Abbreviations: PTU = propylthiouracil.

The exact molecular pathways connecting any observed DILI pathology with an initiating event has yet to be determined. One can only speculate as to how such a pathway or the drug metabolism may differ between humans and rats in the case where the drug-induced pathology is seen in humans but not in rats. It would seem equally speculative to compare drug-induced pathologies seen in the clinic for the compounds described here with the MoAs matching the metabolite profile elicited by those compounds in treated rats. Nonetheless, it is intriguing to note that both phenytoin and flutamide, clinically known for mixed hepatocellular and cholestatic injury in humans, produced metabolite profiles that matched liver MoA patterns corresponding to “cell damage”, “cholestasis”, and “paracetamol-like toxicity”. Zidovudine, clinically known for hepatocellular damage, produced a metabolite profile matching with “paracetamol-like toxicity”. Propylthiouracil, clinically known for hepatocellular damage, matched patterns of “peroxisome proliferation” and “oxidative stress”; captopril treatment, clinically known for mixed hepatocellular-cholestatic damage, matched the pattern of “oxidative stress”; and valproic acid treatment, clinically known for hepatocellular damage, matched the pattern of ”peroxisome proliferation” (Mattes et al., 2014; Zimmerman, 1999). Again, the metabolite profile may only hint at the molecular pathway and resulting pathology.

In conclusion, these results show that the MetaMap®Tox database and associated mechanistic metabolite patterns can detect signals of hepatotoxicity in rats treated with compounds under conditions where signals of hepatotoxicity are not seen with conventional parameters. These compounds include those that have been reported to elicit overt hepatotoxicity in humans, but not in rats.

References
  1. Beger, R.D., Sun, J., Schnackenberg, L.K., 2010. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity. Toxicol Appl Pharmacol 243, 154-166.
  2. Corsini, A., Ganey, P., Ju, C., Kaplowitz, N., Pessayre, D., Roth, R., Watkins, P.B., Albassam, M., Liu, B., Stancic, S., Suter, L., Bortolini, M., 2012. Current challenges and controversies in drug-induced liver injury. Drug Saf 35, 1099-1117.
  3. Horner, S., Ryan, D., Robinson, S., Callander, R., Stamp, K., Roberts, R.A., 2013. Target organ toxicities in studies conducted to support first time in man dosing: an analysis across species and therapy areas. Regul Toxicol Pharmacol 65, 334-343.
  4. Kamp, H., Fabian, E., Groeters, S., Herold, M., Krennrich, G., Looser, R., Mattes, W., Mellert, W., Prokoudine, A., Ruiz-Noppinger, P., Strauss, V., Walk, T., Wiemer, J., van Ravenzwaay, B., 2012. Application of in vivo metabolomics to preclinical/toxicological studies: case study on phenytoin-induced systemic toxicity. Bioanalysis 4, 2291-2301.
  5. Mattes, W.B., Kamp, H.G., Fabian, E., Herold, M., Krennrich, G., Looser, R., Mellert, W., Prokoudine, A., Strauss, V., van Ravenzwaay, B., Walk, T., Naraoka, H., Omura, K., Schuppe-Koistinen, I., Nadanaciva, S., Bush, E.D., Moeller, N., Ruiz-Noppinger, P., Piccoli, S.P., 2013. Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling. BioMed Research International 2013, 12.
  6. Mattes W., Davis K., Fabian E., Greenhaw J., Herold M., Looser R., Mellert W., Groeters S., Marxfeld H., Moeller N., Prokoudine A., van Ravenzwaay B., Strauss V., Walk T., Kamp H., 2014 Detection of Hepatotoxicity Potential with Metabolite Profiling (metabolomics) of Rat Plasma. Toxicology Letters 230 (2014) 467-478
  7. van Ravenzwaay, B., Cunha, G.C., Leibold, E., Looser, R., Mellert, W., Prokoudine, A., Walk, T., Wiemer, J., 2007. The use of metabolomics for the discovery of new biomarkers of effect. Toxicol Lett 172, 21-28.
  8. van Ravenzwaay, B., Herold, M., Kamp, H., Kapp, M.D., Fabian, E., Looser, R., Krennrich, G., Mellert, W., Prokoudine, A., Strauss, V., Walk, T., Wiemer, J., 2012. Metabolomics: a tool for early detection of toxicological effects and an opportunity for biology based grouping of chemicals-from QSAR to QBAR. Mutat Res 746, 144-150.
  9. Zimmerman, H.J., 1999. Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. Lippincott Williams & Wilkins, Philadelphia, pp. 789.


Please note: If you know of any metabolomics research programs, software, databases, statistical methods, meetings, workshops, or training sessions that we should feature in future issues of this newsletter, please email Ian Forsythe at metabolomics.innovation@gmail.com.
 MetaboInterview Icon

MetaboInterview
This section features interviews with prominent researchers in the field of metabolomics. The aim of these interviews is to shed light on metabolomics researchers around the world and give them an opportunity to share their metabolomics story. In this issue, we feature an interview with Paige Lacy.
Paige Lacy
Professor & Director, Pulmonary Research Group, University of Alberta, Edmonton, Canada
Dr. Paige Lacy
Biography

Paige Lacy is Professor of Medicine and Director of the Pulmonary Research Group at the University of Alberta, Edmonton, Alberta, Canada (http://www.prg.ualberta.ca/en/faculty-members/paige-lacy.aspx). She has been based at the University of Alberta since 1997. Her lab’s most significant contributions have been in the area of molecular mechanisms of inflammation and how metabolomics may be applied to our understanding of inflammatory processes. Over the past 18 years she has worked in collaboration with a number of researchers in the field of metabolomics. Her most recent collaborations include Dr. Kathleen Stringer and Dr. Alla Karnovsky at the University of Michigan, and Dr. Ryan McKay at the University of Alberta.

Metabolomics Interview (MN, MetaboNews; PL, Paige Lacy)

 MN: How did you get involved in metabolomics?

PL: I am an immunologist and cell biologist by training, so my background is quite different from that of the usual for researchers working in metabolomics. I first became interested when the National High Field Nuclear Magnetic Resonance Centre (NANUC) was constructed in 2000 alongside the research building that I work in. Because the building housing NANUC was positioned so close to us, my colleagues and I started discussing ways we could analyze clinical samples for specific biomarkers in asthma, cystic fibrosis, and other lung diseases in collaboration with the scientific staff of NANUC. That’s when we first learned about metabolomics as a potential approach for discovering novel biomarkers in lung diseases. Our first study was hypothesis-driven and we determined that it was possible to measure markers of inflammatory cell activation in sputum samples from patients with cystic fibrosis (Magn Reson Med 2004). We were specifically interested in learning if 3’-chlorotyrosine and 3’-bromotyrosine could be detected by NMR analysis of sputum samples, as these would be useful markers of neutrophil and eosinophil activation, respectively. It turned out that 3’-chlorotyrosine could be detected in correlation with neutrophil numbers in sputum samples from patients with cystic fibrosis, but it was trickier to detect 3’-bromotyrosine. This opened up a new field of research for us, where we were able to examine specific biomarkers that are predicted to be elevated in disease. We also realized that we could discover new metabolites in clinical samples that had never been described before using a hypothesis-generating approach.

 MN: What are some of the most exciting aspects of your work in metabolomics?

PL: Probably one of the most exciting aspects is to do with the concept that metabolomics can be applied to the diagnosis of difficult-to-detect diseases. Moreover, it can be applied using highly accessible and non-invasive patient samples such as urine, sputum, saliva, and others, which opens up many avenues for describing biomarkers in disease or in subjects exposed to environmental factors. I am intrigued by the numerous statistical tools that can be applied to complex metabolic profiles, especially PCA and PLS-DA plots as well as ROC curves (see Figure for ROC curve; as shown for mouse models of pneumonia and human pneumonia in J Proteome Res 2009a and 2009b). These tools can be used to measure the sensitivity and specificity of metabolite profiles that show distinctions between control and disease groups, which shows exceptionally robust values when metabolomics is applied to a variety of diseases such as pneumonia. For these reasons, I believe that metabolomics has the potential to revolutionize monitoring of health in the population and diagnosis of diseases in clinical chemistry.

ROC Curve for human pneumonia

MN: What key metabolomics initiatives are you pursuing at your research centre or institute?

 PL: Just recently we started to look at the effects of environmental exposure to air pollutants on the urinary metabolome. The study was only recently funded by the Government of Alberta and we have yet to initiate it. We are hopeful that we will detect differences in subjects exposed to pollution in their work environment as part of their occupation, based on previously published findings.

MN: What is happening in your country in terms of metabolomics?

PL: We are very proud that Canada is a leader in the area of metabolomics, and more specifically that Edmonton, Alberta, is an important site for its contribution to the field of metabolomics. We have built our research on previous achievements by Dr. Brian Sykes, who led the construction of NANUC and is a world-renowned authority on NMR analysis, as well as Dr. David Wishart, who established the world’s first online human metabolome database. Our collaborations with Dr. Carolyn Slupsky, formerly at the University of Alberta and now based at the University of California at Davis in the USA, has also greatly advanced our achievements in this area. I serve as a scientific advisor for Dr. Slupsky’s company, Metabolistics.

MN: How do you see your work in metabolomics being applied today or in the future?

 PL: I hope to see metabolomics become a major diagnostic tool for disease detection and protection, with equivalent funding and investment as that of genomics or proteomics. At present, metabolomics is very much the poor cousin of other ‘omics fields, which is unfortunate. In my opinion, there is far too much funding given towards GWAS studies and other genomic initiatives which fail to deliver a significant return for their investment. The number of diagnostic tests that have arisen from genomic analysis is a tiny percentage of the substantial investment in searches for gene variability leading to disease. In fact, a recent review in Cell suggests that GWAS studies reveal very little of clinical value because of extreme heterogeneity in sequences from the human genome. Population studies have consistently shown that the vast majority of genetic variants have no established biological relevance to disease or clinical utility for prognosis or treatment. But the high public profile that DNA has makes it difficult to push for other important biological molecules in research. In contrast, metabolomics (or metabolite measurements) have already yielded hundreds of clinically useful diagnostic tests. So the potential for metabolomics to become a robust, reliable, and reproducible tool for the diagnosis and prognosis of huge varieties of diseases is untapped and almost completely unrecognized.

MN: As you see it, what are metabolomics' greatest strengths?

PL: One of the greatest strengths of metabolomics is the ability to monitor real-time changes in the physiological or biological profile of an individual by monitoring metabolites in urine, blood, sweat, saliva, and other samples that can be noninvasively (rather than surgically) obtained from human subjects. These changes are possible to monitor within minutes or even seconds. This is simply impossible to achieve using genomics approaches. Gene sequences do not reflect changes as a result of environment exposure or most disease conditions, unless mutations occur as a result of environmental insults such as radiation, since the coding regions of our gene sequences remain largely unchanged over time. Even proteomics analysis only shows modest and comparatively slow changes in protein abundance during environmental exposure or disease conditions.

 MN: What do you see as the greatest barriers for metabolomics?

 PL: Probably the reproducibility of measurements remains the biggest challenge for metabolomics. So far NMR and the hyphenated mass spectroscopy approaches have not been thoroughly validated in multicenter studies to demonstrate reproducibility, and robust comparisons across different sites using statistical tools have yet to be explored.

MN: What improvements, technological or otherwise, need to take place for metabolomics to really take off?

PL: One improvement that we discovered is that NMR instrument calibration is of greater importance that previously appreciated (PLoS One 2014). The measurement of identical urine samples at two different sites revealed differences in quantities of certain metabolites that were related to insufficient calibration of magnets as well as different probe sizes (3 mm vs. 5 mm). We demonstrated this with a radial plot from the study. We also found that different metabolites within the same urine sample, measured at two sites, showed differing variability in measurements. So this suggests that we really need to be careful to validate the measurements of metabolites at different sites and express the variability so that we can determine the impact of the findings more accurately.

MN: How does the future look in terms of funding for metabolomics?

PL: I am always hopeful that increased funding will be made available to researchers in metabolomics and I am confident that governments and funding agencies around the world will find compelling reasons to support research initiatives into this field in the next few decades. The techniques used in metabolomics analyses lend themselves well to high throughput measurements and can easily be applied to clinical care settings.

 MN: What role can metabolomics standards play?

 PL: Standards in metabolomics play a very important role as I believe that this is one of the stumbling blocks for this field compared with genomic and proteomic analyses. There are comparatively few studies that have validated the use of techniques in metabolomics, particularly for NMR vs. mass spectroscopy measurements. I have heard through the grapevine that researchers in general find it much harder to make sense of mass spectroscopy results than they do NMR results, which is likely related to the very high sensitivity that mass spectroscopy has for known as well as unknown metabolites.

 MN: Do you have any other comments that you wish to share about metabolomics?

PL: I think that metabolomics has enormous potential for future applications in both environmental studies and disease diagnosis and prognosis. It’s up to the researchers and clinicians to push for further work in this area and to ensure that the public is made aware of this opportunity.


 Please note: We are open to suggestions for our MetaboInterviews section. Please send suggestions for future interview candidates to Ian Forsythe at metabolomics.innovation@gmail.com.
Metabolomics Current Contents

Metabolomics Current Contents

 This section of MetaboNews is supported by:
LECO Corporation

Recently published papers in metabolomics:

Metabolomics Events

Metabolomics Events
3-6 Mar 2015

Introduction to Integrative Omics
Venue: European Bioinformatics Institute, Hinxton, Cambridgeshire, United Kingdom (Google Maps)

With the increase in the volume of data across the whole spectrum of biology, more researchers are looking to integrate data of different types to inform hypotheses and biological questions. This may be public domain data which researchers themselves have not generated, but can provide added value to datasets derived through their own work. This course will provide participants with an overview of working with a number of 'omics' data types in a more integrated manner; considering both its potential and caveats. The course will focus on the use of public data resources and open access tools for enabling integrated working, with an emphasis on data visualisation.

For more details, visit http://www.ebi.ac.uk/training/course/introduction-integrative-omics.
28 Mar to 1 Apr 2015

Plant Metabolism Session at the ASBMB Annual Meeting
Venue: Boston, Massachusetts

Plant Metabolism will be a 4 day-session at the ASBMB meeting: http://www.asbmb.org/meeting2015/ and http://www.asbmb.org/meetings/annualmeeting2015/sessions/themes/plant/

The abstract submission site is open and accepting abstracts at http://www.asbmb.org/meetings/annualmeeting2015/abstracts/instructions/

Short talks will be chosen from the submitted abstracts. Volunteered abstract submission deadline is THURSDAY, NOVEMBER 6, 2014 (a strict deadline for short talk programming consideration). Plant Metabolism abstracts should be submitted using ASBMB Abstract Topic Categories # 2350 – 2360.

For more information, click here and visit http://www.asbmb.org/meetings/annualmeeting2015/sessions/themes/plant/.
21-22 May 2015

2nd Metabolomics - Advances & Applications in Human Disease Conference
Venue: Boston, Massachusetts

GTCbio is proud to present the 2nd Metabolomics - Advances & Applications in Human Disease Conference, which will be part of The Pan-Omics Summit and takes place May 21-22, 2015 in Boston, MA.

There is still significant human variability in metabolite identification for targets and pathways. These challenges affect the advancement in metabolomics, the use of biomarkers, and its application towards cancer, metabolic disorders, and neurodegenerative diseases. Join us for an event that presents new research and offers networking opportunities with the researchers and scientists who are working on developing clinical assays, connecting the metabolome and the genome, and establishing common quality standards for experimental data.

Sessions:
     I. Advances in Metabolite Markers
     II. Metabolite Identification - Targets and Pathways
     III. Computational Approaches to Assessing the Metabolome
     IV. Technological Advances in Metabolomics

Panel:
     I. Clinical Applications of Metabolomics

For more information, visit https://www.gtcbio.com/conferences/metabolomics-overview.
14-18 Jun 2015

3rd Annual Workshop on Metabolomics
Location: University of Alabama at Birmingham, Birmingham, Alabama, USA

The course is jointly sponsored by the National Institute of General Medical Sciences (NIGMS) as part of the NIH Common Fund Metabolomics Initiative, and the Departments of Chemistry and Pharmacology and Toxicology at University of Alabama at Birmingham (UAB). Those wishing to attend the Workshop should submit their applications by March 27th, 2015. There is fellowship support for young scientists (graduate students and postdocs) to attend the meeting. The workshop is limited to 40 attendees.

The themes in this third year of the workshop are:
  1. Experimental design of a metabolomics experiment
  2. Sample stability and extraction methods
  3. Analytical systems (nuclear magnetic resonance and gas and liquid chromatography-mass spectrometry)
    • Targeted metabolomics
    • Untargeted metabolomics
    • Quantitative metabolomics
  4. Pre-processing of analytical data
  5. Statistical analysis of the data
  6. Metabolite databases – integration with MSMS data
  7. Identification of metabolites
  8. Metabolite pathway analysis
  9. Advances in metabolomics
For further details, visit http://www.uab.edu/proteomics/metabolomics/workshop/workshop_june_2015.php.
15-16 Jun 2015

Informatics and Statistics for Metabolomics (2015)
Location: Downtown Montreal, Quebec, Canada

Course Objectives
 A poster announcing this workshop can be found here.The workshop will cover many topics ranging from understanding metabolomics technologies, data collection and analysis, using pathway databases, performing pathway analysis, conducting univariate and multivariate statistics, working with metabolomic databases and exploring chemical databases. Participants will be given various data sets and short assignments to assist with the learning process.

Target Audience
 This course is intended for graduate students, post-doctoral fellows, clinical fellows and investigators who are interested in learning about both bioinformatic and cheminformatic tools to analyze and interpret metabolomics data.

Prerequisite: Familiarity with R is required. Familiarity can be gained through online activities. You should be familiar with these R concepts (chapters 1-5) or review the past Statistics tutorials provided by CBW.

Apply Now
Award Opportunities

 For further details, visit http://bioinformatics.ca/workshops/2015/informatics-and-statistics-metabolomics-2015.
29 Jun to 2 Jul 2015

Metabolomics 2015: 11th Annual Conference of the International Metabolomics Society
The Official Annual Meeting of the International Metabolomics Society
Location: San Francisco, USA
Venue: Hyatt Regency, Burlingame, USA

You are invited to join us for Metabolomics 2015, the official annual meeting of the Metabolomics Society.

This stunning world-class venue will host the most exciting metabolomics conference of 2015. Your host institution, the University of California, Davis, will gladly welcome scientists from all around the world to feel at home and relax while hearing of the latest innovations and breakthroughs in metabolomics.

Please see the Open Call for Organization of Workshops

Stay abreast of the latest Metabolomics Society news via the Twitter feed on the front page of the website (http://www.metabolomicssociety.org). Also you can follow us on Twitter: Metabolomics Society @MetabolomicsSoc and Metabolomics journal @Metabolomics. And you can visit us on Facebook.

 For further details, visit http://metabolomics2015.org.

Please note: If you know of any metabolomics lectures, meetings, workshops, or training sessions that we should feature in future issues of this newsletter, please email Ian Forsythe (metabolomics.innovation@gmail.com).
Metabolomics Jobs

Metabolomics Jobs

This is a resource for advertising positions in metabolomics. If you have a job you would like posted in this newsletter, please email Ian Forsythe (metabolomics.innovation@gmail.com). Job postings will be carried for a maximum of 4 issues (8 weeks) unless the position is filled prior to that date.

Jobs Offered

Job Title Employer Location Posted Closes Source
Environmental Genomics, Metabolomics and Health
 University of Birmingham
 Birmingham, UK 27-Feb-2015
 March 20, 2015
 University of Birmingham
Postdoctoral Research Fellow, Fernandez Laboratory, School of Chemistry and Biochemistry
 Georgia Institute of Technology
 Atlanta, Georgia, USA 19-Feb-2015
 Until position is filled
 Georgia Institute of Technology
Computational Metabolomics Professor
 Pennsylvania State University
State College, Pennsylvania, USA 26-Jan-2015
Metabolomics Society Jobs
Postdoc – Research Animal Scientist
USDA, Agriculture Research Service, U.S. Meat Animal Research Center		 Clay Center, NE USA 6-Nov-2014
Metabolomics Society Jobs
1 year Master project at the Liggins Institute
 University of Auckland, New Zealand Auckland, New Zealand
 20-Oct-2014
Metabolomics Society Jobs
Applications Support Scientist (f/m) Metabolomics-Lipidomics
 Thermo Fisher Scientific
 EU - European
 16-Jul-2014
Thermo Fisher Scientific


Jobs Wanted

This section is intended for very highly qualified individuals (e.g., lab managers, professors, directors, executives with extensive experience) who are seeking employment in metabolomics. We encourage these individuals to submit their position requests to Ian Forsythe (metabolomics.innovation@gmail.com). Upon review, a limited number of job submissions will be selected for publication in the Jobs Wanted section.
  • There are currently no positions being advertised.


Funding Opportunities
  • The NIH West Coast Metabolomics Center at UC Davis (WCMC) [PDF]
  • The University of Michigan Regional Comprehensive Metabolomics Resource Core (MRC)2 [web page]


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