[ { "start": 0.3, "end": 4.88, "text": "Can we establish unifying principles on data quality in Metabolomics?" }, { "start": 6.52, "end": 15.4, "text": "What pushes scientists to share years of work openly with the community, and how does industry contribute to the way that we do science." }, { "start": 16.58, "end": 18.16, "text": "These are just a few questions." }, { "start": 18.22, "end": 35.58, "text": "we address this episode of The Metabolomist where we dive into the communities that are transformed by Metabolomics." }, { "start": 36.6, "end": 46.46, "text": "I am your host, Alice Limonciel and this year i will engage with scientists who not only use Metabolomix but who leverage it for greater good." }, { "start": 47.72, "end": 57.42, "text": "People know that Metabolomex is a tool which holds promise of transforming our society But also understand to deliver on that promise." }, { "start": 57.94, "end": 60.66, "text": "Metabolomic needs be part something greater." }, { "start": 61.66, "end": 69.82, "text": "projects, networks infrastructures they all form around a common goal and make use of the best tools at their disposal." }, { "start": 70.74, "end": 80.1, "text": "So this year in the podcast I talked to passionate people who build communities through any strategy from grassroot movements to decades of networking." }, { "start": 81.039, "end": 87.94, "text": "join me to discover the creations of these community builders And how Metabolomics is helping them advance their mission." }, { "start": 90.74, "end": 92.28, "text": "Welcome back to The Metabolomist." }, { "start": 92.339, "end": 97.92, "text": "Today, I am joined by Matthew Lewis or Matt Lewis as he is known by most people in the community... Hi Matt!" }, { "start": 97.96, "end": 102.78, "text": "Hello So i'm really happy to welcome you on the podcast." }, { "start": 103.3, "end": 115.66, "text": "One reason it's because we now work together for a few months and have had the pleasure of talking about metabolomics and science with you And I thought that would be great if we share some of those discussions." }, { "start": 117.979, "end": 121.6, "text": "As usual, I would like to begin with a bit of an overview." }, { "start": 147.72, "end": 150.3, "text": "who could possibly take me into their lab." }, { "start": 151.18, "end": 160.7, "text": "And this wonderful woman, a wonderful scientist named Jennifer Nyborg said you're bit young but come back next year and we'll have you!" }, { "start": 161.08, "end": 165.9, "text": "So I did that and i joined her lab the next year got to work with her." }, { "start": 166.86, "end": 175.88, "text": "just an absolutely super team of international scientists Genuinely inspiring and in fact all other things of my life fell away." }, { "start": 176.04, "end": 182.64, "text": "I was supposed to play rugby And do all these other things, and i ended up just living In the lab because i loved it so much." }, { "start": 182.76, "end": 184.28, "text": "i love The people and what we were doing?" }, { "start": 184.38, "end": 184.82, "text": "So It Was a." }, { "start": 185.46, "end": 186.62, "text": "this wasn't the us right." }, { "start": 186.66, "end": 188.34, "text": "This Wasn't colorado or where this" }, { "start": 188.44, "end": 190.8, "text": "is at colorado state university exactly." }, { "start": 191.5, "end": 193.58, "text": "i worked there for For three years." }, { "start": 193.8, "end": 201.46, "text": "i did A masters one year after that And then after that, I was an instructor in the Department of Biochemistry." }, { "start": 203.46, "end": 222.76, "text": "In the course of work at Jenny Nyborg's lab we were doing a lot of chromatographic separations and purifications of protein complexes so ultimately led to some mass spectrometry-based work on proteins." }, { "start": 222.82, "end": 238.42, "text": "Don't tell anyone, but my first mass spectromotory was based on proteins and I just remember really loving how technical and quantitative and analytical mass spectronetary was." }, { "start": 239.5, "end": 248.86, "text": "And you can only do western blots so much And, you know they're very qualitative and after a while that became a bit unsatisfying." }, { "start": 248.94, "end": 254.06, "text": "I mean don't get me wrong i love the work in all but But the techniques were all very qualitative." }, { "start": 254.1, "end": 259.899, "text": "in mass spectrometry was this world of like decimal places an exact measurements and wow just really wowed me." }, { "start": 260.26, "end": 273.099, "text": "i loved it Very much so when the university decided to start a metabolomics program circa two thousand five two thousand six under the leadership of a guy named Phil Ryan." }, { "start": 275.2, "end": 288.14, "text": "I went for it, i thought this is really cool and i loved metabolism from my biochemistry studies and i thought This Is The Perfect Combination Of Background And Chromatography Interest In Metabolism And This Butting Interesting Mass Spectrometry." }, { "start": 289.18, "end": 291.159, "text": "So I Went For That And I Worked Alongside." }, { "start": 291.2, "end": 308.9, "text": "Some Really Wonderful People Later Came To Know Others Who who were very inspiring to work with, and then did some work for or a work that I guess was picked up by Waters Corporation which led recruitment into Imperial College in twenty-ten." }, { "start": 309.68, "end": 319.359, "text": "And things just kind of went from there... That's the whole another explosion of new people lot of talent lots creativity lot inspiration" }, { "start": 320.539, "end": 325.039, "text": "working at the epicenter off this budding world of metabolomics frontier" }, { "start": 326.18, "end": 328.44, "text": "Exactly, I mean working with Elaine Holmes." }, { "start": 328.539, "end": 341.06, "text": "Working with Jeremy Nicholson and then from twenty-twelve onward working with Zoltan Tkachic .I was very lucky to work with all of these great minds ,all this really excellent people good leaders." }, { "start": 341.62, "end": 345.9, "text": "You also worked in one specific structure that is the National Phenom Center." }, { "start": 346.26, "end": 347.06, "text": "What happened there?" }, { "start": 347.56, "end": 352.4, "text": "And especially for for metabolomics lipidomics like what was the purpose?" }, { "start": 355.099, "end": 362.0, "text": "The purpose was a big push into human health, specifically population." }, { "start": 362.38, "end": 373.76, "text": "Health right and it was this joint initiative led by principally by Jeremy Nicholson also other key stakeholders like at Professor Frank Kelly who's now in Imperial College as well." }, { "start": 374.46, "end": 383.88, "text": "And It Was A Big Grant To Reuse Some Of The Instrumentation From London to NT-Twelve Olympics Right?" }, { "start": 383.919, "end": 384.82, "text": "That was a big part of it." }, { "start": 384.88, "end": 405.56, "text": "It's part of the Olympic legacy, and who is intended to tackle societal challenges or diseases that are majorly pressing for human health like neurodegeneration, cardiovascular disease... And those big topics as well serve really excellent local clinical community at Imperial." }, { "start": 405.979, "end": 412.919, "text": "and then more broadly the rest National Phenom Center, and we were very proud to set that up." }, { "start": 413.02, "end": 425.099, "text": "To establish it And I think one of the things That always struck me about is We made a conscious decision not to operate at the bleeding edge Of technology Right?" }, { "start": 425.14, "end": 434.479, "text": "There are other people like again to reference Zoltan Tachkacz who was pushing The Bleeding Edge of Technology in the same department Very lucky to work alongside him." }, { "start": 435.64, "end": 441.46, "text": "But At the phenome center we took A conscious step back From that, and we really focused on standardization." }, { "start": 441.96, "end": 442.18, "text": "Right?" }, { "start": 442.7, "end": 456.799, "text": "And so were I think one of the earlier groups standing on the shoulders of other groups like user met Roy Goodacre and Rick Donnan others Ian Wilson to name a few who are doing large scale studies." }, { "start": 456.919, "end": 466.979, "text": "We've really focused what's needed for large-scale LCMS and NMR based study quality throughput efficiency, how to design the lab for that." }, { "start": 467.02, "end": 468.159, "text": "How do you design workflows?" }, { "start": 468.82, "end": 471.099, "text": "Those were all things very much in scope for us." }, { "start": 472.219, "end": 472.68, "text": "Is it right?" }, { "start": 472.76, "end": 476.24, "text": "after that when they started working with Brooker or maybe there was something in between?" }, { "start": 476.32, "end": 480.7, "text": "so...how did end up moving into industry which is a lot of people?" }, { "start": 481.44, "end": 488.68, "text": "So either big step they took their career and thinking about Yeah," }, { "start": 488.96, "end": 490.859, "text": "I mean it's a going back to Colorado State." }, { "start": 490.979, "end": 503.68, "text": "I mean that I was in the core facility from my I think two thousand six forward and at Imperial College being part of the National national phenome Center Was again like a very big core facility." }, { "start": 503.799, "end": 505.94, "text": "you could think of it In such way right?" }, { "start": 506.039, "end": 512.919, "text": "I think that doesn't do Jeremy Nicholson vision justice but he can take him into that kind away." }, { "start": 513.419, "end": 536.22, "text": "so It is fair to say there was always this one foot in this industrialized world that with a focus on efficiency and the focus on sustainable business, everyone who runs a core facility knows how hard it is to to keep the lights on, you know and make sure that the ins-and-the outs balance in that respect." }, { "start": 536.54, "end": 536.68, "text": "Yeah" }, { "start": 536.72, "end": 538.3, "text": "I think it's a reality" }, { "start": 538.42, "end": 540.8, "text": "of sorry... That is the realty for a lot people." }, { "start": 541.439, "end": 555.22, "text": "so from metabolomics or omics in general core facilities have become one way more accessible just because one group does their expertise work but also do business running this." }, { "start": 557.079, "end": 557.68, "text": "No, not at all." }, { "start": 558.02, "end": 558.819, "text": "You're dead on." }, { "start": 559.04, "end": 565.24, "text": "National Venom Center still has a very talented woman named Lynn Maslin who oversees the business right?" }, { "start": 565.3, "end": 566.22, "text": "So Lynn and I worked together." }, { "start": 566.26, "end": 568.699, "text": "that was an important aspect of them." }, { "start": 568.819, "end": 573.4, "text": "these things shouldn't be overlooked when comparing industry to academia." }, { "start": 574.26, "end": 575.88, "text": "in order make it sustainable." }, { "start": 575.939, "end": 587.12, "text": "we had have someone whose business oriented specifically putting pressure in directions that wouldn't bring a reasonable return on investment, right?" }, { "start": 587.18, "end": 593.3, "text": "So I think we always had a constructive tension Lin and I which was like you know." }, { "start": 593.9, "end": 605.439, "text": "We can do things that we think are innovative but let's also keep it focused on sustainable business Which is good for the people who work there their careers And everything as well." }, { "start": 605.54, "end": 606.42, "text": "so That was great." }, { "start": 606.54, "end": 607.12, "text": "It was really good." }, { "start": 607.18, "end": 618.74, "text": "learning just naturally led towards industry I think, and the tipping point for me was we were working with so many collaborators." }, { "start": 618.819, "end": 631.24, "text": "And working on so many diseases... Working in so many areas of interest.. With so many people.... I think over time at least it became almost overwhelming right?" }, { "start": 632.02, "end": 643.22, "text": "In one meeting you're talking about Alzheimer's disease and then next meeting your'e talking about cardiovascular disease Starts to look the same because that's also not fair." }, { "start": 643.319, "end": 648.42, "text": "But you know some of the like the passions of the people that you're working with who are super." }, { "start": 648.68, "end": 650.42, "text": "I worked with an amazing researcher Who was?" }, { "start": 650.92, "end": 657.96, "text": "Super passionate about diabetes and stratification of diabetes patients beyond type types one And two, and you see that passion." }, { "start": 658.04, "end": 662.3, "text": "but for you The next hour is going to be spent With someone else within equal passion elsewhere." }, { "start": 662.439, "end": 665.1, "text": "You start to think well what's my passion right?" }, { "start": 665.16, "end": 665.28, "text": "What?" }, { "start": 666.439, "end": 667.72, "text": "why do i show up in white?" }, { "start": 667.76, "end": 669.28, "text": "Why Is this so interesting To me?" }, { "start": 670.18, "end": 679.0, "text": "That really gravitated towards building better methods and indeed, better instruments to support what we do." }, { "start": 679.68, "end": 690.98, "text": "And that just naturally led toward industry which over time lead towards a migration over two solutions... We think in terms of solution but an instrument manufacturer." }, { "start": 691.88, "end": 697.56, "text": "And that's how you ended up working at Brooker, where as I hear you explain this path." }, { "start": 697.72, "end": 702.199, "text": "it really fits also with the way we discuss what we do on a daily basis." }, { "start": 702.28, "end": 725.52, "text": "So it really tracks... But so it is interesting for me because one of the reasons why i wanted to invite or let us say have someone from industry and especially from manufacturer some instruments used for metabolomics in the podcast The companies that build the tools we use for Metabolomics are part of the scientific community." }, { "start": 725.699, "end": 736.26, "text": "And I think when you explain your path and how you ended up naturally gravitating towards an instrument vendor, it makes sense but not obvious to everyone." }, { "start": 736.36, "end": 740.84, "text": "so communities is a topic in this year's podcast." }, { "start": 741.579, "end": 746.12, "text": "So what do we get as a scientific community from industry?" }, { "start": 746.28, "end": 749.92, "text": "that academics You know, don't do?" }, { "start": 750.079, "end": 753.84, "text": "that is not the purpose of their work and that's industry contributes." }, { "start": 754.78, "end": 760.34, "text": "It's a very deep question I think for me Is down to enablement." }, { "start": 761.04, "end": 761.939, "text": "right we really?" }, { "start": 762.54, "end": 763.939, "text": "Really focus on enablement." }, { "start": 765.04, "end": 768.76, "text": "remember when i first came To brook or someone asked why you know Why are you doing this?" }, { "start": 769.819, "end": 772.88, "text": "And he said well We drive enabling technologies." }, { "start": 773.12, "end": 774.92, "text": "We make enabling solutions, isn't that cool?" }, { "start": 775.02, "end": 779.18, "text": "And they laughed and said you know, surely it's a party line." }, { "start": 779.38, "end": 780.199, "text": "I thought no!" }, { "start": 780.4, "end": 787.98, "text": "It was not...I was surprised by the reaction because for me really is very genuine attraction to what we're doing here." }, { "start": 789.38, "end": 806.48, "text": "A nice guy named Ian Wilson gave me placard once he used in his lab at AstraZeneca from Humphrey Davey and basically says paraphrasing There's no change in the scientific capabilities of people over the last hundred years." }, { "start": 807.04, "end": 809.64, "text": "But they have access to different tools, right?" }, { "start": 809.72, "end": 818.04, "text": "And that is kind what helps drive things and I didn't understand it honestly at the time he gave this to me." }, { "start": 818.5, "end": 828.16, "text": "but today its really core thats meaningful for us because we had a great privilege of designing tools which help enhance the capabilities." }, { "start": 828.26, "end": 835.86, "text": "Of these very smart, wonderful brilliant people that we're so lucky to work with or call our collaborators are customers right?" }, { "start": 835.96, "end": 838.939, "text": "So for me it's a hundred percent enablement in that respect." }, { "start": 839.46, "end": 850.96, "text": "and by enabling this next generation I mean, we can't forget that they are doing their work to enable clinicians and they're doing their job to enable epidemiologists." }, { "start": 851.0, "end": 858.16, "text": "So it's this kind of really rewarding chain of enablement which helps drive impact in science?" }, { "start": 858.5, "end": 859.04, "text": "That is very neat!" }, { "start": 859.98, "end": 861.42, "text": "Yeah i fully agree thank you." }, { "start": 862.579, "end": 870.199, "text": "so We chose to discuss two papers today And also the topics on those papers tie really nicely into this." }, { "start": 870.96, "end": 877.8, "text": "One is about sharing data that was produced in the international phenome center, you will explain to us why he chose to do that." }, { "start": 878.54, "end": 886.76, "text": "and The other one is about high fidelity data And one of the main issues That everyone knows about In a field of metabolomics." }, { "start": 886.8, "end": 893.439, "text": "There's this comparability confidence How we find methods or agree on methods." }, { "start": 893.5, "end": 894.84, "text": "so We can all move forward." }, { "start": 895.78, "end": 897.68, "text": "So I would start with open platform." }, { "start": 898.079, "end": 901.48, "text": "So it's actually a preprint, you will tell us in the second." }, { "start": 902.939, "end": 904.02, "text": "The eternal preprint?" }, { "start": 904.1, "end": 904.26, "text": "Yes!" }, { "start": 904.76, "end": 909.0, "text": "It is called an open platform for large-scale LCMS based metabolomics." }, { "start": 909.079, "end": 912.72, "text": "and your first author on that preprint from twenty twenty two." }, { "start": 913.66, "end": 922.68, "text": "And so to put it simply You're releasing A lot of data generated with the group at the National Phenom Center In this Preprint." }, { "start": 922.92, "end": 925.96, "text": "Can you explain Why you chose to do that?" }, { "start": 926.0, "end": 933.14, "text": "because often people cling to what they've produced and this is their intellectual property That day, they want to keep it." }, { "start": 933.199, "end": 934.22, "text": "And maybe sell." }, { "start": 934.319, "end": 935.54, "text": "so What was the drive?" }, { "start": 935.6, "end": 936.24, "text": "To Do This for You?" }, { "start": 936.819, "end": 941.3, "text": "yeah So first of all It should be noted that it wasn't my decision." }, { "start": 941.66, "end": 943.439, "text": "It Was The team's Decision." }, { "start": 943.92, "end": 952.26, "text": "the Great Group at AttheNationalPhenomeCenter Wanted to do this in In fact it was a friend of mine suggestion who worked there." }, { "start": 953.62, "end": 958.4, "text": "His name is Gonzalo and he said, you know it would be really cool if we did this in this way." }, { "start": 958.6, "end": 969.18, "text": "everyone wanted to do This massive public disclosure of all the things that we had learned And all the thing's that we have pinned down over the preceding nine or ten years." }, { "start": 969.38, "end": 977.56, "text": "And Gonzalez said We should do It as a preprint and That what allows us To come back to it and revise Revise annotations and Things like that." }, { "start": 977.62, "end": 978.8, "text": "and we thought that's A great idea." }, { "start": 978.96, "end": 985.96, "text": "so Before I left and moved to broker the really, The last thing we did was pull all this information together." }, { "start": 986.12, "end": 986.3, "text": "Right?" }, { "start": 986.34, "end": 988.38, "text": "We cited our other papers." }, { "start": 988.46, "end": 994.3, "text": "a lot of it Was already published but some of it wasn't And specifically things like the SOPs." }, { "start": 994.64, "end": 994.96, "text": "they weren't." }, { "start": 995.1, "end": 996.36, "text": "probably you don't publish S?" }, { "start": 996.439, "end": 1001.78, "text": "O P's in traditional academic way You so we put them on github right." }, { "start": 1001.84, "end": 1008.46, "text": "So-so All of the SOP which took Really smart people A lot Of time To compile." }, { "start": 1010.06, "end": 1017.22, "text": "We had a wonderful person named Verena who I just remember, Verena spending days and days formatting." }, { "start": 1017.56, "end": 1020.5, "text": "Weeks and weeks formatting SOPs right?" }, { "start": 1020.8, "end": 1024.26, "text": "A lot of people involved everyone in the team was involved in building these things." }, { "start": 1026.04, "end": 1028.18, "text": "that's a contribution you think That is a lot work." }, { "start": 1028.56, "end": 1031.42, "text": "let us put out there then the annotations lists Right." }, { "start": 1032.119, "end": 1033.06, "text": "Let s put those out There." }, { "start": 1033.16, "end": 1040.96, "text": "In fact lets Put everything Out There both as a return on the public investment that was made, right?" }, { "start": 1042.0, "end": 1047.72, "text": "But also I think... That was probably ninety percent of the motivation." }, { "start": 1048.319, "end": 1063.62, "text": "Ten percent of interest would be little bit an experiment because we talked about standardization and networks for years prior And i always wondered if value is big enough when people do it." }, { "start": 1063.96, "end": 1066.78, "text": "Because I know people won't standardize through force." }, { "start": 1067.24, "end": 1070.78, "text": "I know, People won't just be told what to do right?" }, { "start": 1070.84, "end": 1075.58, "text": "It's not how innovative especially academic science works at all." }, { "start": 1075.74, "end": 1079.72, "text": "but i was wondered if the value package is big enough." }, { "start": 1079.8, "end": 1082.139, "text": "will people adopt it?" }, { "start": 1082.42, "end": 1083.68, "text": "All the annotations and methods?" }, { "start": 1083.72, "end": 1088.639, "text": "And I think there's some evidence that it has been adopted, right?" }, { "start": 1088.68, "end": 1092.72, "text": "The labs recently opened using the same methods in Germany." }, { "start": 1093.3, "end": 1100.42, "text": "But equally, I think such a disclosure may not be used to its fullest advantage by others in the field." }, { "start": 1100.5, "end": 1105.28, "text": "so ii-I Think It's Been Interesting To See How That's Impacted Or Not Over The Years." }, { "start": 1106.36, "end": 1116.98, "text": "Yes...it's an really interesting topic because of course everyone wants to learn and also exchange you know, the best of the methods or the best off what they've done." }, { "start": 1117.18, "end": 1130.379, "text": "But it's also difficult especially I can imagine when you built your own workflow to say i'm gonna change do something else and maybe that is where too some extents... The workflows are." }, { "start": 1130.42, "end": 1140.46, "text": "the method provided suggested by vendors Can feel like a bit limitations because their limited whatever this group knows." }, { "start": 1140.58, "end": 1154.84, "text": "but To some extent, I guess it's also driving a form of standardization in the field for people who choose to adopt what has been developed in industry and then move from there into make their own version." }, { "start": 1156.32, "end": 1158.379, "text": "Is that development you've seen now?" }, { "start": 1158.9, "end": 1160.46, "text": "You have worked on both sides." }, { "start": 1162.66, "end": 1167.139, "text": "There are certainly people want get going saying please tell me how can do this." }, { "start": 1167.56, "end": 1169.02, "text": "In fact its an expectation." }, { "start": 1170.1, "end": 1174.24, "text": "they say i'm buying these systems I'm buying into your ecosystem." }, { "start": 1174.9, "end": 1176.36, "text": "Uh, also want the methodology?" }, { "start": 1176.5, "end": 1177.379, "text": "I wanna get up and go in" }, { "start": 1177.46, "end": 1177.78, "text": "quickly.\"." }, { "start": 1177.98, "end": 1179.96, "text": "And that's one kind of enablement." }, { "start": 1180.06, "end": 1185.7, "text": "That's- you know us...and other manufacturers." }, { "start": 1185.76, "end": 1191.66, "text": "everyone is trying to support broader communities with perhaps less expert users." }, { "start": 1191.76, "end": 1192.76, "text": "so being able offer." }, { "start": 1192.82, "end": 1207.44, "text": "this is important right but the incentives for a lot use what other people are doing, I don't think that it's really a complete set of incentives." }, { "start": 1207.6, "end": 1220.02, "text": "We have to remember especially in many academic labs the reinvention of The Wheel can get people master thesis and can get PhD thesis and publish papers right?" }, { "start": 1220.1, "end": 1226.92, "text": "You know, you have to take a step back and say why does everyone use their own version of a reversed phase gradient?" }, { "start": 1227.08, "end": 1227.379, "text": "Yeah." }, { "start": 1227.58, "end": 1238.4, "text": "For the last twenty years Why are we suffering such small differences that only serve to undermine value-of-communal resources?" }, { "start": 1238.48, "end": 1241.3, "text": "I'm thinking like retention time databases And things Like That." }, { "start": 1241.94, "end": 1245.3, "text": "i think it's a curiosity Something I've always thought about." }, { "start": 1245.6, "end": 1252.12, "text": "at The end Of the day It is just incentive structure if you believe in uh, incentive structure in free economics." }, { "start": 1252.18, "end": 1260.42, "text": "I don't know if you know the book but it's basically people operate to their incentives and if the incentives are more individualistic i have to get my students through programs." }, { "start": 1262.04, "end": 1263.139, "text": "then that's kind of" }, { "start": 1265.139, "end": 1269.44, "text": "Yeah, and I'm always wondering comparing metabolomics to genomics for example." }, { "start": 1270.139, "end": 1280.5, "text": "And I mean thirty or forty years ago there were many ways to do genomics transcriptomics also like in more homebrew fashions?" }, { "start": 1281.36, "end": 1291.74, "text": "Then at some point there was a crystallization of the technology that led you know, a higher throughput lower cost and all those things that we haven't reached yet for metabolomics." }, { "start": 1291.8, "end": 1296.46, "text": "Whichever way people measure metabolomics also NMR and so on because we talk about mass spec." }, { "start": 1296.54, "end": 1298.08, "text": "but it's not the only way." }, { "start": 1298.16, "end": 1304.139, "text": "But there is still this huge diversity in The Way to acquire the data in Metabolomics." }, { "start": 1305.2, "end": 1310.82, "text": "Absolutely I think often that crystallization moment comes through parallelization right?" }, { "start": 1310.96, "end": 1319.36, "text": "So All of sudden You're doing something in sequence one after the next And all of a sudden eight plex, sixteen plex and it just becomes overwhelming." }, { "start": 1319.4, "end": 1320.879, "text": "The value becomes overwhelming." }, { "start": 1320.96, "end": 1322.0, "text": "so people adopt it." }, { "start": 1322.639, "end": 1333.48, "text": "today we're still you know running things one sample after the next And some people run it faster in Some People Run It Slower but at the end of day someone said this I can't take credit for." }, { "start": 1333.6, "end": 1340.86, "text": "But i love to saying these analytical methods that We all use are like toothbrushes where everyone has their own?" }, { "start": 1341.68, "end": 1343.96, "text": "No One Wants To Use Someone Else's Right?" }, { "start": 1344.26, "end": 1345.96, "text": "That's really, really true." }, { "start": 1346.3, "end": 1353.82, "text": "And I get it from a human nature standpoint but it holds the field back in terms of shared knowledge building on each other." }, { "start": 1355.62, "end": 1359.96, "text": "and there are industries behind this as well like the column chemistry." }, { "start": 1360.26, "end": 1368.96, "text": "industry is also not incentivized to say let's forget all these chemistries and focus just one right." }, { "start": 1369.0, "end": 1370.06, "text": "that will never happen." }, { "start": 1371.46, "end": 1376.94, "text": "so we have at what point metabolism is going to have this crystallization moment?" }, { "start": 1377.02, "end": 1378.84, "text": "And, and what happens there?" }, { "start": 1378.879, "end": 1382.46, "text": "I'm really curious because i think in the end." }, { "start": 1383.24, "end": 1402.74, "text": "In my work also previously was looking a lot into as we're gonna talk about with the second paper so this standardisation aspect of scaling being able to scale the work for example for cohort studies or for exposomic studies For such large projects." }, { "start": 1403.22, "end": 1409.2, "text": "this is really where these standardized methods will make a difference or are making a difference already." }, { "start": 1409.9, "end": 1417.16, "text": "But let's move to the second paper, so this one is from twenty-twentyone with Caroline Sands as first author." }, { "start": 1417.42, "end": 1427.62, "text": "you're The Last Author and the title is Representing the Metabolome With High Fidelity Range and Response As Quality Control Factors in LCMS Based Global Profiling." }, { "start": 1428.32, "end": 1435.879, "text": "You discuss here basically data fidelity maybe now I would say today, confidence also in the data." }, { "start": 1436.32, "end": 1439.66, "text": "But as well as the quantitation it's a perspective paper." }, { "start": 1439.84, "end": 1443.9, "text": "so what was the perspective that your team wanted to push forward?" }, { "start": 1445.54, "end": 1456.36, "text": "The personal interest is this like go back to when i said at the beginning Colorado State working with Western Blots I was trying to quantitate them more than they ever should have been." }, { "start": 1456.44, "end": 1462.42, "text": "And i remember people like jennifer knivework saying you can't scan and quantitate this qualitative data, right?" }, { "start": 1462.9, "end": 1465.139, "text": "This is kind of that same thing." }, { "start": 1465.28, "end": 1487.46, "text": "fifteen twenty years on where we're looking at metabolomics data and were seeing some other weaknesses in it specifically around quantitative fidelity can we just geek out and do a deeper dive, try to make this better?" }, { "start": 1488.8, "end": 1492.72, "text": "This was effectively our COVID lockdown paper for Caroline." }, { "start": 1492.78, "end": 1503.86, "text": "A number of other wonderful people like Elena Chekmaneva Maria Gomez-Romero Gonzalo who I mentioned previously...this is the lockdown geekout!" }, { "start": 1505.379, "end": 1508.18, "text": "That's one reason why i love it so much." }, { "start": 1510.2, "end": 1517.84, "text": "we would love to bring metabolomics into a more serious, reproducible analytical science." }, { "start": 1517.94, "end": 1540.1, "text": "It's not to say it's not serious I'm trying to say that but like...it is somewhat removed from pharma-based bioanalysis which has strict FDA criteria and so quality in metabolomics is usually really relaxed in order to enable discovery In order to enable untargeted workflows and things like that, but does it have?" }, { "start": 1540.18, "end": 1540.54, "text": "To be in?" }, { "start": 1540.62, "end": 1541.7, "text": "is there a better way." }, { "start": 1541.8, "end": 1543.92, "text": "To approach data fidelity and data quality?" }, { "start": 1544.0, "end": 1548.58, "text": "That's exactly what we were trying to get at here And what strategies would we use to do that?" }, { "start": 1548.7, "end": 1550.56, "text": "and What tools do we had to do?" }, { "start": 1550.66, "end": 1552.24, "text": "the pool QCs where did they?" }, { "start": 1553.06, "end": 1555.82, "text": "Where do they really help us and where do they let us down?" }, { "start": 1555.9, "end": 1556.68, "text": "a little bit right?" }, { "start": 1556.76, "end": 1568.78, "text": "so we explored all of those topics in an effort to just push forward The rigor One of the things that I really truly value about it." }, { "start": 1569.18, "end": 1573.379, "text": "There's a guy, like and respect in the field whose name is David Broadhurst." }, { "start": 1573.42, "end": 1577.22, "text": "He's Adam Perth And he described as great but too much." }, { "start": 1579.639, "end": 1582.84, "text": "That exactly where we wanted to be with this." }, { "start": 1586.02, "end": 1586.7, "text": "It is great." }, { "start": 1587.76, "end": 1608.02, "text": "You really put a lot of thought into using real data to exemplify the points that you make, so I encourage people who are curious about maybe philosophy behind what we do and getting perspective as it's called for paper on how this work was done." }, { "start": 1608.94, "end": 1616.3, "text": "but when looking at community perspectives How do we drive this?" }, { "start": 1616.5, "end": 1618.74, "text": "And of course, like you're not in charge of the community." }, { "start": 1618.86, "end": 1620.6, "text": "So you don't have to have the answer for this." }, { "start": 1620.66, "end": 1636.379, "text": "but from your perspective and Of course, your perspective with many years in core facilities which is a special commercial form of metabolomics and now In private sector as well how can these parts of the Community help?" }, { "start": 1637.1, "end": 1640.92, "text": "because they They have this kind of high sample volume." }, { "start": 1640.98, "end": 1650.139, "text": "so like measuring probably more samples than other users of metabolomics in a single year, or enabling the measurement of more samples." }, { "start": 1651.4, "end": 1660.48, "text": "So surely this can lead to some form off making it's more standardized easier?" }, { "start": 1661.52, "end": 1664.2, "text": "How do we do this from this angle?" }, { "start": 1664.3, "end": 1671.86, "text": "to enable the scientific community what they want to do not just tell people that you're going to do but rather say Two" }, { "start": 1675.139, "end": 1675.82, "text": "two concepts." }, { "start": 1675.92, "end": 1677.1, "text": "I think are super important." }, { "start": 1677.5, "end": 1680.36, "text": "like they said earlier the value has to be there." }, { "start": 1680.46, "end": 1689.3, "text": "Otherwise, there's no incentive to adopt and in fact people will In my experience push against standardization in favor of individuality?" }, { "start": 1689.4, "end": 1695.879, "text": "I think there's very reasonable reasons And very much human nature oriented reasons why they would do that." }, { "start": 1695.94, "end": 1701.54, "text": "but if the value is enough They will adapt because they'll say, well gosh I just don't want to recreate that." }, { "start": 1701.66, "end": 1701.86, "text": "Right?" }, { "start": 1701.92, "end": 1706.46, "text": "This is going to advance me two years three years ten years whatever it is and they will adopt them." }, { "start": 1706.5, "end": 1707.44, "text": "They Will Standardize." }, { "start": 1708.5, "end": 1710.879, "text": "That's one aspect To It." }, { "start": 1711.96, "end": 1721.28, "text": "The second Aspect Is Fit For Purpose-ness And this something we thought about very much at the National Phenom Center." }, { "start": 1721.76, "end": 1724.139, "text": "One could argue why did we reinvented the wheel?" }, { "start": 1724.56, "end": 1725.82, "text": "We totally Reinvented the Wheel." }, { "start": 1725.879, "end": 1731.54, "text": "We Reinvented The Methods Ourselves completely guilty of that ourselves." }, { "start": 1732.26, "end": 1738.58, "text": "But we did that in order to serve some needs, they weren't really conventionally met at the time." }, { "start": 1738.879, "end": 1746.22, "text": "so for example We wanted to perform high volume analysis and were not focused on High throughput but focused on high volume." }, { "start": 1747.02, "end": 1751.82, "text": "And what this meant was we want instruments running twenty four seven without interruption." }, { "start": 1753.84, "end": 1763.44, "text": "So a ninety six well plate will run exactly for twenty-four hours if the method is exactly fifteen minutes long, right?" }, { "start": 1764.24, "end": 1769.28, "text": "And so we actually made things longer in order to make our operations more efficient." }, { "start": 1769.54, "end": 1782.92, "text": "If you think about that because at the time We were using maybe twelve minute methods and we really quickly ran into The fact that You don't get on a good cadence and if you're not on a Good cadence you have people coming In the middle of the night or you just have wasted Time." }, { "start": 1783.04, "end": 1794.8, "text": "I remember visiting one lab Who remained nameless person showed me their amazing high throughput system, which was based on technology with two well plates in the auto sampler." }, { "start": 1794.84, "end": 1796.58, "text": "And I said Well what do you do when those are done?" }, { "start": 1796.639, "end": 1799.98, "text": "and they say it's done but that i can run this many samples a day." }, { "start": 1800.76, "end": 1805.32, "text": "You thought why do you run them so fast if there is nothing running?" }, { "start": 1806.48, "end": 1808.04, "text": "That isn't fit for purpose right?" }, { "start": 1808.1, "end": 1816.639, "text": "So often too much focus on throughput Which always seems to have negative impact of data quality." }, { "start": 1816.92, "end": 1817.12, "text": "Right." }, { "start": 1817.34, "end": 1827.48, "text": "The faster you go, of course we try to develop technologies that mitigate that but in like chromatographically the slower you go the better things are." }, { "start": 1828.12, "end": 1832.26, "text": "there's just diminishing returns with going faster and faster." }, { "start": 1832.36, "end": 1837.66, "text": "so I think remembering your approaches should be fit for purpose." }, { "start": 1837.72, "end": 1844.0, "text": "if doing large volume analysis by all means make it high throughput not at a point where undermines quality." }, { "start": 1844.16, "end": 1845.92, "text": "what trying achieve first place?" }, { "start": 1846.92, "end": 1847.92, "text": "That's really interesting." }, { "start": 1848.08, "end": 1853.8, "text": "And that brings for me the question of how do you figure out that value?" }, { "start": 1853.94, "end": 1856.139, "text": "and, um... The purpose is needed?" }, { "start": 1856.379, "end": 1865.48, "text": "So How does a provider of technologies or solutions know what to build For the field." }, { "start": 1865.639, "end": 1870.34, "text": "Is it coincidence Or are there communication channels Can tell us more about this?" }, { "start": 1871.72, "end": 1880.86, "text": "Our collective ears open To community can effectively steer the ship in many meaningful ways, right?" }, { "start": 1880.92, "end": 1881.92, "text": "In many meaningful way." }, { "start": 1882.139, "end": 1893.06, "text": "I think that job we sometimes discuss is trying to look through or past what people say they want and try to really interpret what they need be successful." }, { "start": 1893.18, "end": 1896.02, "text": "So there's a little bit of an interpretation step There." }, { "start": 1896.68, "end": 1902.1, "text": "People may say i want this And if you hear it enough You might think What are you saying?" }, { "start": 1902.379, "end": 1902.5, "text": "Oh!" }, { "start": 1902.62, "end": 1906.26, "text": "You're actually saying this to be successful." }, { "start": 1906.36, "end": 1910.26, "text": "And that's so, you know there is a little magic and work done here." }, { "start": 1911.44, "end": 1913.16, "text": "it not just direct one-to-one." }, { "start": 1913.24, "end": 1913.3, "text": "oh!" }, { "start": 1913.36, "end": 1913.78, "text": "You want this." }, { "start": 1913.86, "end": 1920.74, "text": "we will deliver this but ultimately the field at the helm of the ship right?" }, { "start": 1921.76, "end": 1923.58, "text": "What best thing can do?" }, { "start": 1923.98, "end": 1925.82, "text": "design innovative solutions." }, { "start": 1929.36, "end": 1941.5, "text": "So making the unmet needs known coming together and saying these are critical on met needs in them, then letting industry or Industry academia partnerships innovate to fill those." }, { "start": 1941.82, "end": 1943.22, "text": "That's kind of the name of the game." }, { "start": 1943.8, "end": 1946.36, "text": "I think that's that's the important good way forward." }, { "start": 1946.42, "end": 1950.0, "text": "And in terms of the value like the magnitude of the volume?" }, { "start": 1950.52, "end": 1952.96, "text": "Think you have to be willing to give certain things away." }, { "start": 1954.42, "end": 1955.24, "text": "You really have to." }, { "start": 1957.26, "end": 1960.28, "text": "We'll help you interpret your data more or interpret your annotations." }, { "start": 1960.4, "end": 1967.52, "text": "More we have to be able To, to help people in that way In order to drive progress." }, { "start": 1967.66, "end": 1969.68, "text": "I think and That's that goes for the whole community?" }, { "start": 1969.74, "end": 1972.66, "text": "That's not really an industry only perspective." }, { "start": 1972.96, "end": 1979.139, "text": "i Think everyone has a role to play in that industry academia networks collaborative networks core facilities." }, { "start": 1980.18, "end": 1994.16, "text": "Yeah when You look at The the metabolomics Community today I'm sure, i think we all have our perspectives of like our pet projects or the fields that we think and no metabolomics will be helpful with." }, { "start": 1994.46, "end": 2002.78, "text": "When you think about the future of that technology where do you see it being the most relevant in five ten years?" }, { "start": 2002.98, "end": 2007.32, "text": "Being optimistic... That is not going to take too long for it to become hyper-relevant!" }, { "start": 2009.36, "end": 2013.879, "text": "The field and what it promises that can achieve like I really, by promise." }, { "start": 2014.34, "end": 2018.02, "text": "Like the idea of boundless possibility?" }, { "start": 2020.18, "end": 2036.92, "text": "So for me some interesting applications are in naturally harder to reach areas using metabolomics brain sciences, brain being a naturally fairly inaccessible organ." }, { "start": 2037.54, "end": 2037.86, "text": "Right?" }, { "start": 2038.6, "end": 2038.76, "text": "And" }, { "start": 2039.16, "end": 2039.22, "text": "so" }, { "start": 2040.24, "end": 2043.4, "text": "you know okay like we can all take blood and that's one thing." }, { "start": 2043.44, "end": 2055.699, "text": "but for prevention diagnosis prognostics treatment guided treatment especially of diseases in conditions they are hard to pin down any other way." }, { "start": 2056.44, "end": 2067.82, "text": "the mental health aspect the chemical signatures where metabolomics can potentially give us a lens that is otherwise very hard to find." }, { "start": 2067.9, "end": 2076.06, "text": "There just isn't another way into these types of diseases and organs, I think that's interesting for me." }, { "start": 2077.04, "end": 2088.12, "text": "the forever frontier is exposomics though really i think The world around us Is chemically changed more than we can possibly grasp?" }, { "start": 2090.48, "end": 2100.759, "text": "One of the most exciting things we're doing as a technology innovator is that, where providing systems now which are able to shed light on how-on the extent to which that's true." }, { "start": 2102.04, "end": 2105.04, "text": "Driving this kind of age of realization around." }, { "start": 2105.18, "end": 2109.08, "text": "oh my gosh there... There's PFOS in water!" }, { "start": 2110.86, "end": 2122.3, "text": "And every time we burned wood, there was a paper recently where were just releasing lead back into the air from wood that I don't know presumably absorbed it over decades of letted petrol use." }, { "start": 2122.38, "end": 2122.56, "text": "Right?" }, { "start": 2122.86, "end": 2127.64, "text": "It's this is every new paper on this topic as an oh my gosh moment!" }, { "start": 2128.6, "end": 2136.4, "text": "It's really an enlightening moment and i think we need to keep driving technologies that enable us to do." }, { "start": 2137.06, "end": 2139.0, "text": "And then link it back to human health, right?" }, { "start": 2139.04, "end": 2140.56, "text": "That's why I mean its the forever frontier." }, { "start": 2140.64, "end": 2152.62, "text": "because of chemical diversity we're pumping into environment is massive and influence on endogenous metabolism in human biochemistry always going be a study." }, { "start": 2153.22, "end": 2156.5, "text": "so i don't think its final frontier but really its forever frontier" }, { "start": 2165.36, "end": 2167.68, "text": "or similar methods you're going to use to measure the exposome." }, { "start": 2167.759, "end": 2185.22, "text": "So, you can use parts of the knowledge that you've built studying metabolomics, lipidomics and then expands that... ...to look at both the exposure and the impact it has on an individual or group of individuals with similar or parallel measurements." }, { "start": 2185.58, "end": 2191.62, "text": "And this also I think from the perspective of the technologies and building those technologies." }, { "start": 2191.66, "end": 2194.06, "text": "there's a lot there that could be leveraged." }, { "start": 2194.9, "end": 2202.38, "text": "They don't have to reinvent the wheel again when you do expose them, like go look at different chemical classes but already know how to do a lot of it." }, { "start": 2203.92, "end": 2204.32, "text": "That's true!" }, { "start": 2204.44, "end": 2208.259, "text": "I think that all comes down getting this sample in right?" }, { "start": 2208.36, "end": 2217.18, "text": "So whether humans can be reduced to liquid extracts pretty easily... you know." }, { "start": 2217.28, "end": 2218.62, "text": "But, there's other things right?" }, { "start": 2219.52, "end": 2231.759, "text": "There is certainly air which is an area where we're moving into now and all that it just like a different sampling technique maybe different ionization techniques And different frequency of sampling." }, { "start": 2231.88, "end": 2233.82, "text": "I think thats'a big thing as well." }, { "start": 2234.1, "end": 2244.08, "text": "The metabolome can be very dynamic but the air is super transient so actually have to sample more." }, { "start": 2245.12, "end": 2248.28, "text": "What in that field they call high time resolution, right?" }, { "start": 2248.36, "end": 2249.32, "text": "So yeah." }, { "start": 2249.44, "end": 2253.14, "text": "It's all variations on a theme but fit for purpose." }, { "start": 2253.48, "end": 2257.02, "text": "I think it comes back to whether the technologies are fit-for-purpose." }, { "start": 2258.72, "end": 2265.8, "text": "so Are there any other aspects of the metabolomics community or your work that you would like to discuss?" }, { "start": 2268.1, "end": 2278.82, "text": "i Think one of the most interesting things that i've seen In The last five years Or so is how data quality unifies broadly." }, { "start": 2280.62, "end": 2290.84, "text": "Long time established expert users and novice researchers, especially a shout out to the MQAC consortium." }, { "start": 2291.86, "end": 2292.759, "text": "they are." }, { "start": 2293.16, "end": 2294.86, "text": "those calls are amazing right." }, { "start": 2294.92, "end": 2301.7, "text": "you have this equal footing for for big names and people just starting out." }, { "start": 2301.8, "end": 2309.62, "text": "And I don't know, it seems like this really great healthy unifying topic which brings people who may otherwise not be working together." }, { "start": 2310.12, "end": 2312.16, "text": "so i've loved seeing that." }, { "start": 2313.0, "end": 2315.759, "text": "what the NQAC guys are doing is incredible!" }, { "start": 2316.6, "end": 2319.94, "text": "I love being a part of but its community driven." }, { "start": 2320.0, "end": 2323.9, "text": "there's no single person at the helm, which is itself interesting." }, { "start": 2323.94, "end": 2325.28, "text": "It seems to work really well." }, { "start": 2325.42, "end": 2329.56, "text": "so I don't know if you're listening and not involved in that." }, { "start": 2330.08, "end": 2332.46, "text": "get involved because it's really cool!" }, { "start": 2333.2, "end": 2335.32, "text": "i can think of many other things like that." }, { "start": 2336.02, "end": 2339.08, "text": "um...that have had impact on bridging people." }, { "start": 2339.42, "end": 2345.86, "text": "its just good to see in an era of reproducibility crises or everything quality being in focus." }, { "start": 2347.52, "end": 2352.8, "text": "So this brings us our last question What's your favorite metabolite and why?" }, { "start": 2354.54, "end": 2365.4, "text": "I think my favourite, in terms of the one that i've thought most about or worked with over last years would be cysteine." }, { "start": 2365.44, "end": 2367.34, "text": "Why" }, { "start": 2367.52, "end": 2369.3, "text": "cysteines?" }, { "start": 2369.38, "end": 2381.5, "text": "Well back in eighteen ten there was a paper by I hope i don't mix these things up." }, { "start": 2382.1, "end": 2387.24, "text": "William Hyde-Walliston, now you know this is off the fly because he just asked me his question." }, { "start": 2387.34, "end": 2387.94, "text": "Yes yes!" }, { "start": 2388.88, "end": 2397.08, "text": "William Hyed Walliston had a paper on a kidney stone that was of an unknown composition." }, { "start": 2398.16, "end": 2407.98, "text": "back in eighteen ten... In very early nineteen hundreds by that point they understood it as made out of material called cysteine right?" }, { "start": 2408.62, "end": 2416.04, "text": "Assisting very insoluble in water and that's why it was forming kidney stones, the urine of people with certain inborn errors." }, { "start": 2416.66, "end": 2423.08, "text": "And in fact, cystineuria became one of the original inborn areas of metabolism described by Archibald Garrett." }, { "start": 2423.14, "end": 2426.04, "text": "in nineteen whatever oh five or something like that." }, { "start": 2426.28, "end": 2459.28, "text": "um...and That kind of history and the curiosity around that is really interwoven into my very early um, desire to understand biochemistry more and I It is a very long story around that which i won't get into now but that was Very impactful in terms of how chemistry has direct impact on On life and human health and opening the idea of inborn errors of metabolism Which really brings one Into an appreciation for the impact of metabolism." }, { "start": 2459.58, "end": 2463.9, "text": "And you can see from there How one may become enamored with the whole thing?" }, { "start": 2465.58, "end": 2467.62, "text": "Studying that right trying to elucidate." }, { "start": 2467.66, "end": 2470.08, "text": "That but like what an amazing amino acid." }, { "start": 2470.14, "end": 2476.68, "text": "disulfide bridges important for For protein structure on the port and four all different types of chemistry." }, { "start": 2478.24, "end": 2478.64, "text": "You know it." }, { "start": 2479.1, "end": 2486.34, "text": "glutathione reservoir is An important concept in metabolism, and it's all because of Sistine disulfides Right?" }, { "start": 2486.4, "end": 2491.06, "text": "Let's let's really me I don't even frankly know how to say had a say it properly." }, { "start": 2491.16, "end": 2492.72, "text": "Is it sistine as its sustain?" }, { "start": 2493.5, "end": 2494.3, "text": "What do you call the Dysophyte?" }, { "start": 2494.34, "end": 2494.44, "text": "You're" }, { "start": 2494.48, "end": 2495.9, "text": "asking me, your native speaker." }, { "start": 2496.88, "end": 2498.04, "text": "Yeah I don't know!" }, { "start": 2498.759, "end": 2499.88, "text": "These are things we write a lot but don't" }, { "start": 2499.92, "end": 2500.18, "text": "talk about it." }, { "start": 2500.22, "end": 2501.12, "text": "Dysulfide bond...I dunno." }, { "start": 2501.48, "end": 2504.259, "text": "yeah yeah yeah mm-hmm Mm-hmm" }, { "start": 2504.38, "end": 2505.16, "text": "Two sisteins." }, { "start": 2505.28, "end": 2508.66, "text": "one of there's an extra E in one of them right It's all kind of fascinating" }, { "start": 2510.54, "end": 2514.6, "text": "i think Both from The Chemistry and From The Spelling Point Of View." }, { "start": 2516.22, "end": 2520.08, "text": "Thanks Thank you for being on the podcast today who was lovely to speak with you." }, { "start": 2521.0, "end": 2521.78, "text": "Oh its my pleasure." }, { "start": 2521.84, "end": 2522.18, "text": "thank you." }, { "start": 2523.84, "end": 2531.4, "text": "Thank you for listening to this episode of The Metabolomist, where we explored one the many communities that leverage metabolomics." }, { "start": 2544.32, "end": 2550.7, "text": "Until then, I wish you to get to use Metabolomics with the same passion and dedication as my guest today." }, { "start": 2551.3, "end": 2557.32, "text": "And don't hesitate reach out to me on LinkedIn at Alisle Montiel with your thoughts for this episode!" } ]