Jamie Timmons
@metapredict
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OMICS-Data-DrugDiscovery-Metabolism-Aging. Odd humour reflects my fusion of Scots-Irish & Jewish 🧬 😲
Camden Town, London
Joined May 2011
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TEN FIREWORK MAYBELLINE
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Pinned Tweet
@tjstokes5
@SnyderShot
Seems so! Amazing
@StanfordMed
can't afford fibre to search the internet?
Replication of our general observation in human tissues. Not to cite In this case is fraud Id say
@NatureAging
?
(his ontology methods look flawed on 1st inspection🙄)
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“no differences in total daily energy expenditure or resting metabolic rate related to the timing of calorie distribution, and no difference in weight loss”
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Science Forum: Ten common statistical mistakes to watch out for when writing or reviewing a manuscript
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"exercise-induced browning in rodent iWAT was most likely an artefact"
A must read for all. Crucial examples of how lab-temp housed mice produce dramatic but potentially irrelevant Nature/Cell papers.
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A must read. To deliberately ignore the issue = choosing to p-value hack ur OMIC pathway analysis to falsely claim “significance”
It’s the OMICS equiv of using fake blots!
@MicrobiomDigest
@ForBetterSci
>80% of articles were problematic.
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@ashleyruba
worst. advice. ever.
Doing a PhD? It’s not a job - if you don’t have a passion for it at 22y & able to sacrifice/dedicate to it, then it’s not for you (and there are probably better things to do in life)
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One of my favourite all time quotes. I just need to keep it in mind more often.
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Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates
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Jeopardy!
“If five large studies all yield VERY different answers to what is the constitutively expressed protein coding transcriptome in skeletal muscle”
What is RNAseq?
#Myotwitter
#MotrPAC
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@sophie_astrof
@MicrobiomDigest
@ucl
State who it was? the only way forward is to identify these people. I had a clinical collaborator (samples) take a new draft manuscript (we wrote) & pass it as grant app in her name. Bente Klarlund Pedersen. Arne Astrup reported her previously for plagiarism. No action.
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By ignoring 5 decades of research on glycogen (including its role as a sink for a variety of kinases/proteins) you can get a nature paper
"Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines"
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Real Science. Effects of Two Years of Calorie Restriction on Aerobic Capacity and Muscle Strength (in Humans)
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"Mechanism preventing mROS generation switched off with age in short-lived small mammals" Crucial component of an anti-aging program & contributor to the mid-life 'switch' transcriptome response in humans?
#aging
#ROS
#longevity
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Essential reading for anyone working with small clinical data-sets At what sample size do correlations stabilize? ?
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Just editing the proofs of our 21-page (duh) genome-wide coding and non-coding RNA map of fasting human insulin sensitivity. >1,000 muscle samples, treatment-responses and striking consistency from GWAS DNA, to RNA, to the biochemistry of metabolic disease. 8yrs, job done.
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Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise
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"Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults"
Is this a case of "too much signaling" is undesirable or just that Metformins main benefits in T2DM are liver mediated with some down-sides elsewhere?
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More evidence from Myers that "cardiorespiratory fitness" (which is highly genetically determined) rather than PA is key to the link between mortality and "exercise".
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High-intensity interval exercise training for public health: a big HIT or shall we HIT it on the head?
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"Longevity‐related molecular pathways are subject to midlife “switch” in humans" by
@univmiami
@UniofNottingham
@uniofjyvaskyla
@DukeU
Funded by
@The_MRC
NIA
@Alzheimers_NIH
and
@ERC_Research
#mTOR
#Neuromuscular
#Alzheimer
's disease
@AgingCell
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@MicrobiomDigest
Time to approach Gates et al and start an independent institute (perpetual funding, independent oversight board and some good lawyers) for the investigation of science fraud and dishonesty?
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1/ Our contribution to drug repositioning (DR) for metabolic disease (MD)
In HUMANS Insulin resistance (IR) in muscle & adipose shares COMMON molecular pathways & COMMON treatment responses (n= >2,000 samples).
@mackinprof
@eLIFE
@JPTK_TechBio
@chvolmar
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Less mTOR signalling more muscle?
http://t.co/xIZjSwMB0k
fits with human high-responders
http://t.co/nHiSTuOIIF
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Monster 60-page article, 1,012 muscle biopsy based OMIC model of human insulin sensitivity completed today. Time for a beverage I believe 🙃
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@JoachimSchork
Nice, important - but if I recall it’s not really a paradox (nice discussion of it in action here - ).
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Preparing for the mother of spatial transcriptomics experiment
@mackinprof
@tjstokes5
@MACleod_JC
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@TEnglishSport
@patjohnburke
Using a definition that makes little sense. If we had 11 international goal keepers on the pitch would that be a stronger or weaker team?
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@StevenSalzberg1
@chelysheva_i
Aside from differences in database content, impacting on mapping gene IDs & enrichment stats (& the stats methods) most GO results I encounter are false due to flawed reference BG list. Journals ignoring issue - we cover some of the issues here.
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Since Lindholm et al 8yr ago RNAseq - applied to human muscle - has produced erroneous data & incorrect claims of superior performance
After great efforts by
@tjstokes5
@HowardCen
and colleagues we explain some of the why's
#MyoTwitter
#Transcriptomics
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So often key, older articles, are not cited, perhaps to imply novelty
You would think that citing prior evidence clearly & hence reporting ‘reproducibility’ would be considered a good thing.
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What a year! Got married (!) and did DNA test to reveal I'm 50% Ashkenazi Jewish (Lithuanian/Russia) - family moved to Glasgow in the 1870's
@Ancestry
Followed our (much ignored) 1st robust tissue IR OMIC model
@NAR_Open
with a very exciting Age study out 6th June
@AgingCell
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A road map of therapeutic targets to mimic exercise or a tour de force in selective citations, debunked targets & a homage to irreproducible research?
#exercise
#drugdiscovery
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Step aside Indiana Jones "A Harvard scientist is telling fictitious stories about aging that go nowhere other than continuing hype as legendary as anything in Herodotus"
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Time-efficient HIT protocol in (out-bred) adult humans at-risk of T2DM but note Figure 4
@JPhysiol
@DiabetologiaJnl
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resistance exercise modulates microRNA expression. Blood not reflecting the muscle
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@sophie_astrof
@MicrobiomDigest
@ucl
It’s impossible to negotiate with these types of people. They have a psychopathic level of self belief.
List them and return to your science. The system will eventually wake up to this stuff, thanks to
@MicrobiomDigest
et al
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Current epigenetic clocks do not provide strong benefits in predicting the decline of physical functioning at least during 3yr follow-up period and restricted age-range.
i.e. can't be applied to n=1 and inform any better than asking that person their age
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60-70% of the key long term disease predictor - VO2max - is familial/genetic in young healthy.
Implications? Failure to account for VO2max in cross-sectional genetic/genomic studies of adult metabolic disease 🤦♂️
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One reason why science is failing captured in eloquent prose
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Generously
@nature
have started to publish confirmation studies! So there are nonlinear aging signatures - including mitochondrial genes - and many are ~common to multiple tissue types😱
#aging
#mitochondria
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“GPs to prescribe cycling in new obesity strategy” - You could not make this cr*p up? New effective strategy? Or a middle-class patronising sound bite that ignores social issues, poverty & real underlying drivers of ill health?
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11years today! The haircuts getting more interesting son! 💚🥳
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The (properly measured) RNA model of human insulin resistance fits with genomics (DNA) and biochemistry of metabolic disease. Free access here
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Over 20yr since we released the first genome-wide transcriptome view on exercise adapting human muscle. The extracellular matrix was a dominant feature. This seems to be consistent with the new exercise science…
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Adipose UCP1 negative correlates with training-weight-loss. Nice job Asif &
@mackinprof
#MoTrPAC
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@tangming2005
@maxhertan
It’s a made up concept based on a epidemiological correlation with DNAm markers correlated to chronological age (that’s in causal experiments doesn’t change in a predictable manner or at all)….
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@tp590
@CzSam00
@LeptihnLab
Complete garbage published in MDPI (from areas I work in). Seen articles rejected (completely flawed stats) bounce into MDPI within weeks! Let’s not kid ourselves on here. System flawed and MDPI aint at the top end of the rigour charts….
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Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference
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enzymatic dissociation on tissue induces an aberrant ex vivo gene expression signature which is prevalent in published literature and can substantially confound downstream single cell analyses
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Looks like my friend
@DrMichaelMosley
is gone 😢. RIP michael, a charismatic and delightful man.
@bbchealth
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Diet drinks/food trigger weight gain & diabetes, says newspaper, psychologists & wee fairies...
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FGF21 weight-loss in non-human primates
Weak AT UCP1 signal lost during treatment (no "browning") as
@mackinprof
found in humans doi: 10.3945/ajcn.116.132563
RNA-seq failed in muscle (long discussion but predictable)
NHP & Mouse differ.
#Obesity
#Diabetes
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"In adjusted analysis, high response (to short term training) = greater CRF at 10y follow-up independent of other characteristics" Kraus et al start to illustrate the potential importance of CR responsiveness to ET. J Am Heart As
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Possibly another reason to stop calling "euglycaemic insulin clamps" gold standard (for anything other than insulin clamps).
Oral and intravenous glucose administration elicit opposing microvascular blood flow responses in skeletal muscle
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Finally available on PubMed
If you want reliable quantitative bulk transcriptomics, consider Clariom D with nano WT kit - not stochastic Illumina short-read seq. If you want advanced maps for modelling the Clariom D data dm me.
#aging
#RNA
#lncRNA
Jeopardy!
“If five large studies all yield VERY different answers to what is the constitutively expressed protein coding transcriptome in skeletal muscle”
What is RNAseq?
#Myotwitter
#MotrPAC
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For anyone serious about epigenetics and DNAm studies these are must-read articles on the approach to analysis, the substantial failure of a large % of the illumina technology & how to make the best of the subset of reliable probes
#Aging
#Epigenetics
#Muscle
#Diabetes
DNA methylation, key issues before u get excited
"DNAm Aging Algorithms Contain Unreliable measurement"
Key learning: 450Kchip-wide databases not sensible
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Reversine enhanced insulin signalling in human skeletal myoblasts
Independent vallidation of one of top scoring hits in our drug-repurposing IR model (
@eLIFE
2022)
@mackinprof
@tjstokes5
@wildtypehuman
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skeletal muscle FNDC5 gene expression and irisin "release" not regulated by exercise or related to health
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@dgmacarthur
Fraction of GWAS loci validated to a causal mechanism (or indeed established to reflect 1 gene or just 1 phenotype) so far?
Ridiculous to suggest hypothesis based science - across the breadth of science - needs to die out. The facts are modeling data is fraught with biases
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If you are interested in BDNF - the non-secreted protein not from myofibrils (not stored in granules, just like other myokines*) then its worth reading this JBC article on BDNF in human blood
(*in many geographical locations)
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“ "Garbage in, garbage out" is the unbreakable law of computation, and as I've said before, machine-learning approaches turbocharge this to previously unseen levels”
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Exercise and cognition - another
#EIM
#ACSM
myth.
"small exercise-related benefits became substantially smaller after accounting for key moderators, and negligible after correcting for publication bias"
@ProfRobHoward
& the tortoises can relax
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“only one-quarter of more than 5500 lab animals used over a 2-year period at one university in the Netherlands ended up being mentioned in a scientific paper afterward”
Most animals used in biomedical experiments are not accounted for in published papers, a first-of-its-kind study suggests
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Functional high intensity exercise training ameliorates insulin resistance and cardiometabolic risk factors in type 2 diabetes - Fealy - - Experimental Physiology - Wiley Online Library
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@mackinprof
The Truth is out!! (swapping to a meat substitute was found to potentially add four years to your life, compared to eating red meat every day). Or does it just feel longer?
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Not that we really need more evidence that short-read RNA-seq is broken but it just keeps rolling in...
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Nice review on adipose tissue adaptability re obesity by Philipp Scherer: drives home the commonality with muscle responding to chronic exercise
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@AlejoFraticelli
qPCR was already poor for validating 2nd Gen bulk seq (as evidenced by the SEQ consortium 2016 Nature Biotech paper (which itself is full of errors). Validating an omic study is done by running a second independent omic study (rarely done for scRNAseq….)
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Latest data: >non protein-coding genes expressed in human skeletal muscle than coding. Makes u think.
@mackinprof
@stirproftip
@Sale_ExNut
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As predicted by some: In vivo reprogramming leads to premature death due to hepatic and intestinal failure. | bioRxiv
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@arjunrajlab
Nae…. the amount of energy to refute bs is too high. there’s more idea’s available to follow up - rigorously - than scientists on the planet. Less, slower and more reliable would make everybody’s life easier and more pleasant
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Imagine if we were all limited to only 17 publications? Lots of careful thought and time would be taken, we’d remove the sillly business model of the publishing houses & improve science as everyone could keep up
Seems to be consistent with ‘impact’ in architecture
Antoni Gaudí was born 172 years ago today.
He's one of the most beloved architects in the world, and that makes sense — his style is utterly unique.
But Gaudí only designed 17 buildings...
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Cool mitochondrial study - Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent | The EMBO Journal
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I fear you have been hacked Diabetes UK - these tweets are embarrassing us metabolism people in front of our neuroscience colleagues. Please get it stopped 🙏
@Diabetescouk
@pash22
@ProfRobHoward
Eating kiwi can improve your mental health in less than a week
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It’s worth pausing for thought when the number of co-authors greatly exceeds the sample size.
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@FrezzaLab
It’s really always been understood to be a fuel in various settings to various cell types (at least since I was an undergraduate). Strange that
@SpringerNature
think this is news worthy metabolism.
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Microtubules important for insulin resistant skeletal muscle via GLUT4
Fits with our clinical-based multi-gene insulin resistance assay, that found drugs that disrupt microtubles also disrupt the 120-gene IR signature
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A Randomized Community-based Exercise Training Trial with good compliance in African American Men: AT + RT for modification of insulin resistance.
#Exercise
#Diabetes
#nonresponder
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Next time some bro/bro-et tells u exercise will stop aging send them this. Exercise is good for controlling T2DM risk, modulating physical capacity etc - but the causality relationship between exercise phenotypes & health is MUCH more complex.
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A very comprehensive study - were you surprised at the lack of overlap between rats and human multi-tissue aging signatures or human metabolic disease?
@davidjglassMD
@biogerontology
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Human GDF15 knockouts - "Here we show the absence of an overt phenotype in human GDF15 loss-of-function carriers".
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That was fast. Structural basis for the recognition of the SARS-CoV-2 by full-length human ACE2
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An important article. “extracellular vesicles-borne miRNAs do not act as effectors of cell-to-cell communication”
Moreover, multiple miRNAs target each gene, at ‘relatively’ high [] relative to target. EV never going deliver - next myokine fable?
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(In) "accuracy in Wrist-Worn, Sensor-Based Measurements of heart rate & energy expenditure"
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An essential read - a snap shot of the impact of rapid expansion of ‘doing fast science’ - these errors contaminate data mining/aggregation biology tools that are blind to this type of error (or worse)
Our
@biorxivpreprint
by Yasunori Park et al with
@Cell_Detective
@gcabanac
@PranujanP
describing 712 human gene research papers with wrongly identified DNA/ RNA sequences is now published
@LSAjournal
A thread...🧵1/8
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“Stay fit to fight the virus, say medics”. Hours of exercise biology taught to medics? ~Nil. Evidence that you can pre-hab for pneumonia & degenerative lungs in the ICU? Nil.
@bbchealthupdate
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Exercise training for 5y on all cause mortality in older adults. Control Group not scientific but a pragmatic control (left to follow PA guidelines). moderate intensity training did worse - HIT did better than control (Mortality) - neither significant.
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@Neuro_Skeptic
@PubPeer
This is largely misdirection. The reason for "overwhelming" is lack of rigorous action taken against fraudulent researchers when caught. Too little too late.
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Always curious when another magic mouse myokine appears (Fibcd1) & is claimed to cure cachexia (esp when the article goes uncited)
Guess what? FIBCD1 isn't expressed in cultured human muscle cells or detectable in a human muscle biopsy profile
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Think that lncRNA are low-expressed and each only found in few cell types. Think again - you are probably studying an RNA-seq library artefact
#noncoding
#transcriptomics
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Effects of GLP-1 Infusion Upon Whole-body Glucose Uptake and Skeletal Muscle Perfusion During Fed-state in Older Men
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@SashaGusevPosts
In complex biology topics it can take 4-6 weeks just to review the literature / so these figures are way off (unless one writes and ignores the current status of the field). Some fields involve > new articles a week.
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When your claim your age-acceleration trick reduces muscle strength by 20% but u fail to correct for 20% lower lean mass you are just playing games....
Matters Arising: The Information Theory of Aging Has Not Been Tested
@SSRN
@cellpressnews
Sneak Peek
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30°C mice housing revealed sexual dimorphism in the white adipose tissue proteome that was largely absent in animals housed at 24°C.
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