[Metabolomics] Some good news

O'Sullivan, John F.,M.D.,Ph.D. JFOSULLIVAN at mgh.harvard.edu
Tue Apr 12 10:21:17 AEST 2016


Hello all, 

Just wanted to share some good news I’ve had, which is probably relevant to all. I was recently very fortunate to have a breakthrough using non-targeted metabolomics. As you all know, there has been very little success to date using this method. There are only a handful of examples where a novel discovery using non-targeted metabolomic profiling has gone on to be validated. 

The reason it worked in this case was threefold: 

1. incorporating orthogonal data (GWAS in this case)
2. concentrating on a gene that coded for an enzyme, thereby putting the unknown metabolite in a precursor / product association
3. predicting likely structure based on #2 above and harnessing the expertise of chemists!

We then synthesize and purified the compound, and loaded it onto our high-throughput LC/MS platform. We then validated its association with this phenotype in other cohorts. 


So here’s what I learned:

1. doing as much orthogonal profiling in the same patients is key for novel discovery (genetic, metabolomic, proteomic, multiple phenotypic parameters). Incorporating this data makes all the difference. Trying to identify metabolites from a list of potential matches for an unknown mass has never worked for me - more info is essential, and an enzymatic association is huge. 

Also, the metabolite we identified wasn’t on ANY of the metabolite databases (HMDB, Metlin) or chemical databases (Pubchem, Chemspider), so these databases are far from complete. 
That’s why I’m so excited to hear from David James about upcoming studies at the CPC that will incorporate all these types of data in the same cohort.

2. Input from Chemists is essential. Here, I was lucky we had an organic chemist in the lab, and that we closely collaborate with a synthetic chemist. So I hope to identify the same expertise when I get to the CPC, and work closely with them!


I’ll share exact details once we get this paper out, which will probably be around the time I move to Sydney!

Looking forward to getting to Sydney and meeting up with you guys!

All the best, 

John








> On Mar 21, 2016, at 9:00 PM, metabolomics-request at mailman.sydney.edu.au wrote:
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> Today's Topics:
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>   1. Re: Symposium Tue 15th March 2pm @ CPC: From Paddock to
>      (Metabolomics) Lab (Ben Crossett)
> 
> 
> ----------------------------------------------------------------------
> 
> Message: 1
> Date: Mon, 21 Mar 2016 07:35:44 +0000
> From: Ben Crossett <ben.crossett at sydney.edu.au>
> To: "Metabolomics at mailman.sydney.edu.au"
> 	<Metabolomics at mailman.sydney.edu.au>
> Cc: Stuart Cordwell <stuart.cordwell at sydney.edu.au>,	David James
> 	<david.james at sydney.edu.au>
> Subject: Re: [Metabolomics] Symposium Tue 15th March 2pm @ CPC: From
> 	Paddock to (Metabolomics) Lab
> Message-ID: <91043E40EC58C34BB59CEF09BC71C1870118085268 at ex-mbx-pro-06>
> Content-Type: text/plain; charset="iso-8859-1"
> 
> Hi Folks,
> 
> I know there were several of you who couldn't make it to last week's metabolomics meeting.  Don't fear, you haven't missed out completely.  Anthony Dona and Charlie Warren - two talks which have a particularly broad appeal, have uploaded their slides to the drop box.
> 
> If you don't have access to the drop box let me know and I will send you an invite.
> 
> We have also been having issues with people being unable to subscribe to the mailing list. It is a tricky problem where it appears to accept your subscription request, but never adds you to the list.  I have cc'ed a couple of people who aren't currently subscribed.  If you know of any colleges who are having trouble subscribing either contact ICT directly for assistance or let me know.
> 
> Kind regards,
> 
> Ben
> 
> 
> From: metabolomics-bounces at mailman.sydney.edu.au [mailto:metabolomics-bounces at mailman.sydney.edu.au] On Behalf Of Ben Crossett
> Sent: Tuesday, 8 March 2016 5:30 PM
> To: Metabolomics at mailman.sydney.edu.au
> Subject: Re: [Metabolomics] Symposium Tue 15th March 2pm @ CPC: From Paddock to (Metabolomics) Lab
> 
> Hi Folks,
> 
> Here is an provisional schedule for the metabolomics meeting next week:
> 
> Discovery and Translational Metabolomics Applied to Livestock
> Charles Perkins Centre - Flexible Dry Space 2 (Dry Teaching 1.3)
> Tuesday 15 March 2016
> 
> Schedule
> 2:00        Introduction: Michael D'Occhio
> 2:10        Pietro Baruselli: Livestock challenges and opportunities for metabolomics in Brasil (15+5)
> 2:30        Anthony Dona: NMR metabolomics (15+5)
> 2:50        Samantha Connolly:  LC/MS lipidomics (15+5)
> 3:10        Tea break
> 3:40        Charlie Warren: Metabolomics of plant-soil interactions (15+5)
> 4:00        Michael D'Occhio: Metabolomics in cattle
> 4:20        General discussion and scoping of opportunities
> 5:00        Refreshments at the Forest Lodge
> 
> Please RSVP for catering purposes by 12noon this Friday.
> 
> Kind regards,
> 
> Ben
> From: metabolomics-bounces at mailman.sydney.edu.au<mailto:metabolomics-bounces at mailman.sydney.edu.au> [mailto:metabolomics-bounces at mailman.sydney.edu.au] On Behalf Of Ben Crossett
> Sent: Thursday, 3 March 2016 1:33 PM
> To: Metabolomics at mailman.sydney.edu.au<mailto:Metabolomics at mailman.sydney.edu.au>
> Subject: [Metabolomics] Symposium Tue 15th March 2pm @ CPC: From Paddock to (Metabolomics) Lab
> 
> Dear Metabolomics Researchers,
> 
> S?o Paulo State Research Foundation (FAPESP) has a global engagement program.  As part of this program, Prof Michael D'Occhio has a collaboration with Professor Fl?vio Vieira Meirelles from Sao Paulo focusing on building metabolomics capacity in livestock research.
> 
> A group from Sao Paulo will be visiting USyd for a week starting on the 14th March, so we are planning the next metabolomics meeting to coincide with the visit.  This is the draft program:
> 
> When: Tuesday 14th March, starting at 2pm
> Where: 'Flexible Dry Space 2' (aka Dry Teaching 1.3 on the door sign), Ground floor of The Hub, (CPC) Building.
> What: 2 sessions of  3 x 15 min talks with plenty of time for discussion. There will be a half hour tea break in the middle and for those that want, refreshments at the Forest Lodge<http://forestlodgehotel.com.au/> from 5pm.
> 
> We have speakers for 3 of the slots, but I would like to hear from anyone who would like to give a update on their work.  It could be from those in the large animal/livestock space, but as there is much overlap between this work and what many of you are doing in the biomedical area don't be shy about volunteering.
> 
> Please RSVP if you can make the meeting by Fri 11th March so I can finalised numbers for the tea break catering.
> 
> Kind regards,
> 
> Ben
> 
> Dr Ben Crossett | Manager
> Mass Spectrometry Core Facility
> DVC Research
> 
> THE UNIVERSITY OF SYDNEY
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