Covid, Phase II. Commonsense is the order of the day.
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Spursex
Alert Team
'Scientific Breakthrough': AI Program Solves Decades-long ‘protein Folding Problem’
In a breakthrough, DeepMind’s biennial Critical Assessment of protein Structure Prediction (CASP) was able to detect how proteins fold up using AI 'AlphaFold'.
Written By
Zaini Majeed
ed decades-long 'protein folding problem’ after it mapped out their 2D structures and distinguished between the different types of proteins. For more than 50-years, scientists were unable to decode biology’s one of the biggest challenges that could help in the development of treatments and drug effectiveness. On November 30, however, a London-based Google-owned artificial lab DeepMind announced that its program AlphaFold was now able to detect many shapes of the proteins that could accelerate research in fields of drug design, treating diseases, and environmental sustainability.
In a breakthrough, DeepMind’s biennial Critical Assessment of protein Structure Prediction (CASP) was able to detect how the proteins fold up by the thorough assessment of several experimentally determined protein structures. In total, there are approximately 200 million known proteins that exist. Researchers from the 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP14) solved the 1994 riddle by creating an attention-based neural network system that was trained end-to-end to interpret the structures using the latest version of AI AlphaFold.
[Two examples of targets in the free modelling category. Credit: Deepmind site]
'Trained' on 170,000 protein structures
“AI system developed strong predictions of the underlying physical structure of the protein and is able to determine highly-accurate structures in a matter of days,” scientists informed in a release. They added, that AlphaFold could also predict “which parts of each predicted protein structure were reliable.” AlphaFold was trained on 170,000 protein structures, generated an average accuracy score of 92.4 out of 100 in prediction. “This computational work represents a stunning advance on the protein-folding problem, a 50-year-old grand challenge in biology,” said President of the Royal Society Venki Ramakrishnan. “It will be exciting to see the many ways in which it will fundamentally change biological research,” he added.
In a breakthrough, DeepMind’s biennial Critical Assessment of protein Structure Prediction (CASP) was able to detect how proteins fold up using AI 'AlphaFold'.
Written By
Zaini Majeed
ed decades-long 'protein folding problem’ after it mapped out their 2D structures and distinguished between the different types of proteins. For more than 50-years, scientists were unable to decode biology’s one of the biggest challenges that could help in the development of treatments and drug effectiveness. On November 30, however, a London-based Google-owned artificial lab DeepMind announced that its program AlphaFold was now able to detect many shapes of the proteins that could accelerate research in fields of drug design, treating diseases, and environmental sustainability.
“Figuring out what shapes proteins fold into is known as the protein folding problem, and has stood as a grand challenge in biology for the past 50 years,” the AI lab informed in a release.
It added, that the large complex molecules composed of amino acids were comprised in all life forms’ supporting systems, including in COVID-19 disease-causing viruses SRAS-coV-2 and in cancer cells.
It added, that the large complex molecules composed of amino acids were comprised in all life forms’ supporting systems, including in COVID-19 disease-causing viruses SRAS-coV-2 and in cancer cells.
In a breakthrough, DeepMind’s biennial Critical Assessment of protein Structure Prediction (CASP) was able to detect how the proteins fold up by the thorough assessment of several experimentally determined protein structures. In total, there are approximately 200 million known proteins that exist. Researchers from the 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP14) solved the 1994 riddle by creating an attention-based neural network system that was trained end-to-end to interpret the structures using the latest version of AI AlphaFold.
[Two examples of targets in the free modelling category. Credit: Deepmind site]
'Trained' on 170,000 protein structures
“AI system developed strong predictions of the underlying physical structure of the protein and is able to determine highly-accurate structures in a matter of days,” scientists informed in a release. They added, that AlphaFold could also predict “which parts of each predicted protein structure were reliable.” AlphaFold was trained on 170,000 protein structures, generated an average accuracy score of 92.4 out of 100 in prediction. “This computational work represents a stunning advance on the protein-folding problem, a 50-year-old grand challenge in biology,” said President of the Royal Society Venki Ramakrishnan. “It will be exciting to see the many ways in which it will fundamentally change biological research,” he added.
Pompey Yid
Vital Champions League
Thanks for that EX, but here we go again, not your fault you are trying thankyou, the lady said CRPS, probably referring to CHRONIC Regional Pain Syndrome, which is as common as muck, obviously sorry for those that suffer with that ailment, that's fine, but my lady suffers with COMPLEX R P S, the problem we are finding is that the NHS uses CRPS, which is 100% wrong and we feel its there way to push it under the carpet, not RSD/CRPS its full title, and majority of Doctors refer to CHRONIC, which they all know about, and not COMPLEX which is a major difference.
Examples, if Me/Mrs PY or her Carer, phone say 111 or 999, and we get a Doctor, if we mention Mrs PY's ailment as CRPS, that Doctor does then get it so wrong taking it as CHRONIC, thus we then say no its COMPLEX, followed by stuttering um um, every bloody time, so as you can probably guess we always say RSD/CRPS, Reflex Sympathetic Dystrophy/Complex Regional Pain Syndrome, some Doc's react excellently some totally crap. By the way the NHS website is total shit, American Hope website brilliant, even Mrs PY Cardiac Surgeon said the same recently.
Also Mrs PY has been to Pain Management Clinics, they are a complete waste of time for COMPLEX R P S sufferers, but very good for CHRONIC R P S.
Oh Yes! in my original post I did say my wife has NO immune system, so what is the answer.
Thanks again for all you have done mate it is most appreciated..
Spursex
Alert Team
Ok, made one last attempt to see if it would help, asked the question and phrased it exactly as you have i.e. Complex RPS and for what it's worth was told that you need to go to the best there is and I was told it is this man:
https://www.imperial.nhs.uk/consultant-directory/christopher-jenner
Apparently, he also runs a private clinic in Harley street, but is also the UK's leading expert in Complex RPS - which from the paper I read below does suggest that it does have a link to the immune system.
https://www.expertwitnessjournal.co...-crps-be-defined-as-a-psychological-condition
Pompey Yid
Vital Champions League
That's brilliant EX, thank you so much, oh! and thanks for listening, it is much appreciated.
Spursex
Alert Team
I think if you reach out to him, he may well be as interested as you are in deciding what if any risks the vaccine might have for her. But go via his NHS presence, I suspect (but do not know how engaging he would be in his private role?)
Harry-Kari
Vital 1st Team Regular
That was fascinating although I am reminded of what one of my old IT bosses, who was not really into IT, said on returning from a technical presentation on disk drives...he said “ One instinctively knew that the language being used was English because one recognised individual words”....anyway I got the basic drift, but with something that complex you really need to be familiar with the vocabulary deployed....thanks though.'Scientific Breakthrough': AI Program Solves Decades-long ‘protein Folding Problem’
In a breakthrough, DeepMind’s biennial Critical Assessment of protein Structure Prediction (CASP) was able to detect how proteins fold up using AI 'AlphaFold'.
Written By
Zaini Majeed
ed decades-long 'protein folding problem’ after it mapped out their 2D structures and distinguished between the different types of proteins. For more than 50-years, scientists were unable to decode biology’s one of the biggest challenges that could help in the development of treatments and drug effectiveness. On November 30, however, a London-based Google-owned artificial lab DeepMind announced that its program AlphaFold was now able to detect many shapes of the proteins that could accelerate research in fields of drug design, treating diseases, and environmental sustainability.
“Figuring out what shapes proteins fold into is known as the protein folding problem, and has stood as a grand challenge in biology for the past 50 years,” the AI lab informed in a release.It added, that the large complex molecules composed of amino acids were comprised in all life forms’ supporting systems, including in COVID-19 disease-causing viruses SRAS-coV-2 and in cancer cells.
In a breakthrough, DeepMind’s biennial Critical Assessment of protein Structure Prediction (CASP) was able to detect how the proteins fold up by the thorough assessment of several experimentally determined protein structures. In total, there are approximately 200 million known proteins that exist. Researchers from the 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP14) solved the 1994 riddle by creating an attention-based neural network system that was trained end-to-end to interpret the structures using the latest version of AI AlphaFold.
[Two examples of targets in the free modelling category. Credit: Deepmind site]
'Trained' on 170,000 protein structures
“AI system developed strong predictions of the underlying physical structure of the protein and is able to determine highly-accurate structures in a matter of days,” scientists informed in a release. They added, that AlphaFold could also predict “which parts of each predicted protein structure were reliable.” AlphaFold was trained on 170,000 protein structures, generated an average accuracy score of 92.4 out of 100 in prediction. “This computational work represents a stunning advance on the protein-folding problem, a 50-year-old grand challenge in biology,” said President of the Royal Society Venki Ramakrishnan. “It will be exciting to see the many ways in which it will fundamentally change biological research,” he added.
Pompey Yid
Vital Champions League
EX I have just had a quick look at the 2nd website, the first thing I noticed was it talks of Complex RPS in an arm, thus a limb, of which there are about 30k sufferers in Britain, which is say a back, legs or arms, individual, Mrs PY's problem is that she is the only Sufferer of this ailment that is "Whole Body" every bloody where in the this country, from what we can gather, is that Mrs PY is one of only about 5 worldwide.
Thanks again for your endeavour's mate.
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Spursex
Alert Team
Then you may find you are of even more interest to the doctor I was told about - the less well-known a condition is, often that's the one's that will get their attention.
After another chat with a scientist who knows of him, I'm hoping he'll take an interest - but you'll have to do all the running on it - the best way to start is to get her GP to write a referral / covering letter/email to him and then pursue a follow-up after you know it's got to his clinic etc.
Hopefully, he is the man who will help.
Pompey Yid
Vital Champions League
A big thanks again EX, Mrs PY is chuffed to bits and we will start tomorrow.
Harry-Kari
Vital 1st Team Regular
Doctor on BBC News this morning said an article in the Lancet about the Oxford vaccine said that the trial group that received the accidental dosing regime that resulted in an “up to “ 90% efficacy did not contain anyone in the older age groups and they are now scrambling to conduct further tests...
It doesn’t build confidence in their testing regime that the 90% was only obtained by accident and then that result wasn’t achieved across all age groups, plus they don’t know why the 90% dosing regime seems to work.
I hope that it does prove effective and these questions can be answered but it’s not impressive.
It doesn’t build confidence in their testing regime that the 90% was only obtained by accident and then that result wasn’t achieved across all age groups, plus they don’t know why the 90% dosing regime seems to work.
I hope that it does prove effective and these questions can be answered but it’s not impressive.
Spursex
Alert Team
Afraid that's all true, I read the data yesterday as well; and sometimes lucky accidents happen, and the half dose was a mistake by the manufacturers, and the small cohort that had it, had an amazing result. So far the further work suggests that a smaller dose first followed by a full planned dose causes the immune system to 'prime' itself and then when it does receive more, it goes into full production - they will have to test further to ascertain why.
So this small cohort had an average age of around 45 so it doesn't exclude older recipients from having the same reaction, but it's now an unknown. And no one is letting them make any assumptions.
So, I agree, confidence has been dented - but if it all works, then a delay of a couple of months might well prove beneficial - even if it was by accident.
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Harry-Kari
Vital 1st Team Regular
I do so want this to succeed EX, just very disappointed...fingers crossed they can produce the necessary good results soon but as you say these things take time to be reliable.
Spursex
Alert Team
Oxford COVID-19 Vaccine Trial Results Mixed
Tim Locke
December 08, 2020
Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.
Phase 3 interim trial results from the Oxford/AstraZeneca vaccine have just been published in The Lancet. Previously, interim results were issued in a press release.
In today's paper, for participants who received two standard doses, vaccine efficacy was 62.1%.
In participants who received a low dose followed by a standard dose, efficacy was 90.0%.
This was described as "intriguingly high compared with the other findings in the study. Although there is a possibility that chance might play a part in such divergent results."
Professor Andrew Pollard, director of the Oxford Vaccine Group, Department of Paediatrics, University of Oxford, told a news briefing hosted by the Science Media Centre that the half dose, full dose approach that gave the best results wasn't planned. He dismissed concerns about the age of participants in that group saying the result "doesn't appear to be an age phenomenon".
Overall vaccine efficacy across both groups was 70.4%.
Regulators and UK vaccination advisers would have to assess which regimen might be selected for approval, Prof Pollard said.
The vaccine was found to be safe, the authors said, with only three out of 23,745 participants over a median of 3.4 months experiencing serious adverse events that were possibly related to a vaccine; one in the vaccine arm, one in the control arm, and one in a participant who remains masked to group allocation. All participants have recovered or are recovering, and remain in the trial.
The paper said: "A case of transverse myelitis was reported 14 days after ChAdOx1 nCoV-19 booster vaccination as being possibly related to vaccination, with the independent neurological committee considering the most likely diagnosis to be of an idiopathic, short segment, spinal cord demyelination."
Prof Pollard said: "I think today is an important landmark for us because the data package that is in this paper is being put forward to regulators to consider and to scrutinise so there's these two different aspects of scrutiny, there's the scientific peer review for publication, and also the regulatory processes which I'm sure we'll hear more about in the weeks ahead."
Professor Sarah Gilbert, Jenner Institute, Nuffield Department of Medicine, University of Oxford, said: "This is a really good day in the UK. This is probably the best day we've had in 2020. Not only today are we seeing the first rollout of NHS vaccinations against COVID-19, from our side we're able to present to you our data in a full peer reviewed publication."
Reaction
In a linked comment, Dr Maria Deloria Knoll and Dr Chizoba Wonodi, Johns Hopkins Bloomberg School of Public Health, USA, who were not involved in the study, said: "Despite the outstanding questions and challenges in delivering these vaccines, it is hard not to be excited about these findings and now the existence of three safe and efficacious COVID-19 vaccines, with 57 more in clinical trials."
Professor Stephen Evans, professor of pharmacoepidemiology, London School of Hygiene & Tropical Medicine, commented: "These results reflect the headlines given in previous press releases, but with both a fuller explanation of what was done and more detail around the uncertainty in the estimates of efficacy.
"The unfortunate [half dose] measurement technique problem that occurred with some doses produced in Italy is going to be seen by some as raising questions about this trial. It is clear however, that national and international regulators were fully apprised of what had happened and a plan for analysis was determined prior to knowledge of the results."
Spursex
Alert Team
Some expert comment on the above: Interestingly, it seems Phizer and moderna have published only selective data and seen some poor AR's as well?!
Dr. Christopher Pickin 1 hour ago
These results raise some very interesting problems.
Firstly, they have been published and are there warts and all for critical comment.. this is the way it should be.
Secondly, Oxford have been following their participants with tests.. how has that distorted the results.. if you level the playing field, how does Oxford then stack up against Pfizer.
Next, we are already seeing adverse reactions to the Pfizer vaccine.. was this picked up in the trials? If not, why not? And if it was, then we should have been told and have had the data to be aware of the problems in advance.
Finally, we understand viral vectors that are going to be eliminated when immunity kicks in.. we do not understand the long term implications of mRNA vaccines.. particularly when given to hyper-immune individuals.
We need to see the data. The data should have been published before the vaccine was given regulatory approval.. we are now heading into a situation which could have negative effects on people's willingness to be vaccinated. That would be an absolute disaster.
Dr. jayadave shakher 3 hours ago
1. efficacy calculation and analysis is different from Pfizer and Moderna, these looked at only symptomatic patients and analysed them.
2. half dose in Oxford vaccine may have been trial breach but these cases are separated out in the analysis.
3. Oxford study is published in peer reviewed journal for everyone to analyse and see. Have Pfizer and Moderna published full data yet?
4. The important aspect for the population at large which may have to depend on Oxford vaccine or other similar affordable vaccines - the questions are 1. it is over 99% safe to take it 2.Does it have over 60% efficacy - if the answers to the above are yes, then we should embrace it. If not then, experts can analyse and tell us what are the concerns.
5. as one can see, it is difficult to conduct this type of study in a short term across the globe and we have to give credit to Oxford for doing the trial under these circumstances and publishing the data.
6. any vaccine has rare side effects - flu vaccine and others, so the question is is oxford vaccine different from existing vaccine in these rare neurological adverse events??
7. what is the long term safety data of Pfizer and Moderna - just over 60 days?
8. What are the long term effects of mRNA vaccine over years??
9. finally it all comes down to risks vs benefits
10. in a sceptical way between the devil and deep not so blue sea!!! do we have a choice as HCPs, protect oneself from taking vaccine because of whatever may be our reason or wider community - Ethical question??
Dr. Dana Ludwig 5 hours ago
The half dose was the first injection
Dr. Eric Lawes 2 hours ago
@DR. Dana Ludwig rejection of the Oxford vaccine in favour of the two alternatives depends on the endpoints that are considered desirable. If contracting the disease is the only endpoint then the two mRNA vaccines win. If the end points are no serious disease, hospitalisation or death then there is no real difference between the vaccines. Zero recipients of the Oxford vaccine were hospitalised and none died. Perfectly good in my opinion
Dr. Christopher Pickin 42 minutes ago
@DR. Dana Ludwig are they really better? Pfizer and Moderna do not seem to have tested in the same way as Oxford and we don't yet understand how that might have distorted the results. Plus Oxford have published and held their hands up to tell us about the mistake. Does that not reassure you? Pfizer and the MHRA have certainly not warned us that vaccine can cause anaphylactoid reactions which is far more dangerous in terms of public trust. There must be a reason why the will not publish.
Donna Gerber 9 hours ago
The fact that none of these reports is defining “efficacy” is most disturbing. The average person interprets this as the ability of the vaccine to prevent transmission. It is a horrible that the WHO has redefined this term!
Arnold Layne 3 hours ago
No I would say that the average person views the results as acquisition and not transmission for that is what concerns the individual
Dr. Christopher Pickin 32 minutes ago
@donna Gerber no.. the efficacy of a vaccine is in preventing infection. Suppression of transmission does follow but with a lag. The WHO is perfectly correct. Vaccines do not prevent you catching a virus.. but they do stop you getting sick and dying.
Transmission is a lot more complicated.. if you do get the virus, it is quickly suppressed and you don't get the high viral loads and extended period of infectivity. Plus, although we can pick up a viral signature, it is questionable if it implies infectivity.
Sorry.. you are being misled by people with evil intent in spreading confusion about vaccination.
Dr. Christopher Pickin 1 hour ago
These results raise some very interesting problems.
Firstly, they have been published and are there warts and all for critical comment.. this is the way it should be.
Secondly, Oxford have been following their participants with tests.. how has that distorted the results.. if you level the playing field, how does Oxford then stack up against Pfizer.
Next, we are already seeing adverse reactions to the Pfizer vaccine.. was this picked up in the trials? If not, why not? And if it was, then we should have been told and have had the data to be aware of the problems in advance.
Finally, we understand viral vectors that are going to be eliminated when immunity kicks in.. we do not understand the long term implications of mRNA vaccines.. particularly when given to hyper-immune individuals.
We need to see the data. The data should have been published before the vaccine was given regulatory approval.. we are now heading into a situation which could have negative effects on people's willingness to be vaccinated. That would be an absolute disaster.
Dr. jayadave shakher 3 hours ago
1. efficacy calculation and analysis is different from Pfizer and Moderna, these looked at only symptomatic patients and analysed them.
2. half dose in Oxford vaccine may have been trial breach but these cases are separated out in the analysis.
3. Oxford study is published in peer reviewed journal for everyone to analyse and see. Have Pfizer and Moderna published full data yet?
4. The important aspect for the population at large which may have to depend on Oxford vaccine or other similar affordable vaccines - the questions are 1. it is over 99% safe to take it 2.Does it have over 60% efficacy - if the answers to the above are yes, then we should embrace it. If not then, experts can analyse and tell us what are the concerns.
5. as one can see, it is difficult to conduct this type of study in a short term across the globe and we have to give credit to Oxford for doing the trial under these circumstances and publishing the data.
6. any vaccine has rare side effects - flu vaccine and others, so the question is is oxford vaccine different from existing vaccine in these rare neurological adverse events??
7. what is the long term safety data of Pfizer and Moderna - just over 60 days?
8. What are the long term effects of mRNA vaccine over years??
9. finally it all comes down to risks vs benefits
10. in a sceptical way between the devil and deep not so blue sea!!! do we have a choice as HCPs, protect oneself from taking vaccine because of whatever may be our reason or wider community - Ethical question??
Dr. Dana Ludwig 5 hours ago
The half dose was the first injection
Dr. Eric Lawes 2 hours ago
@DR. Dana Ludwig rejection of the Oxford vaccine in favour of the two alternatives depends on the endpoints that are considered desirable. If contracting the disease is the only endpoint then the two mRNA vaccines win. If the end points are no serious disease, hospitalisation or death then there is no real difference between the vaccines. Zero recipients of the Oxford vaccine were hospitalised and none died. Perfectly good in my opinion
Dr. Christopher Pickin 42 minutes ago
@DR. Dana Ludwig are they really better? Pfizer and Moderna do not seem to have tested in the same way as Oxford and we don't yet understand how that might have distorted the results. Plus Oxford have published and held their hands up to tell us about the mistake. Does that not reassure you? Pfizer and the MHRA have certainly not warned us that vaccine can cause anaphylactoid reactions which is far more dangerous in terms of public trust. There must be a reason why the will not publish.
Donna Gerber 9 hours ago
The fact that none of these reports is defining “efficacy” is most disturbing. The average person interprets this as the ability of the vaccine to prevent transmission. It is a horrible that the WHO has redefined this term!
Arnold Layne 3 hours ago
No I would say that the average person views the results as acquisition and not transmission for that is what concerns the individual
Dr. Christopher Pickin 32 minutes ago
@donna Gerber no.. the efficacy of a vaccine is in preventing infection. Suppression of transmission does follow but with a lag. The WHO is perfectly correct. Vaccines do not prevent you catching a virus.. but they do stop you getting sick and dying.
Transmission is a lot more complicated.. if you do get the virus, it is quickly suppressed and you don't get the high viral loads and extended period of infectivity. Plus, although we can pick up a viral signature, it is questionable if it implies infectivity.
Sorry.. you are being misled by people with evil intent in spreading confusion about vaccination.
Thanks both. This is the article Nick suggested in case anyone is interested https://www.theguardian.com/world/2...val-compares-between-the-uk-europe-and-the-us
So it seems (unless I am mistaken) that the US differs from the UK/European approach by waiting until all data has been collected on the study before starting to analyse and work back to check everything is correct. Whereas the European/UK approach is to work with the study and look at each stage of data rather than waiting to do it in one go and so as a result are a few steps ahead. It also seems like the FDA takes a less trusting approach and so will take a deeper dive into the raw data thus requiring more time before approval.
Where the UK approach differs from that of EMA is how the UK has used existing emergency protocols to fast track this vaccine via temporary approval. The EMA doesn't want to do this so is waiting for more long term authorization that requires more checks so will likely only get approved later in December.
I guess the dilemma is; is the risk of distributing an emergency approved vaccine to those in the vulnerable categories greater than the risk of those groups becoming infected with a decease that we have no cure for.
Spursex
Alert Team
It's also about the crude part as well - cost benefit analysis; early roll out may well save the UK government around #12 billion per month - i.e. hospitalisation and other national emergency costs, and thats without calculating costs/benefits to the economy, which might well be substantial.
I hate to be brutal but a few that might die or have a long term issue because of a vaccine are all deemed to be acceptable risks by just about everyone involved in making these decisions - they could easily be off-set by the many hundreds/thousands it might save.
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That is indeed worrying. Especially in this age of relatively large doubt of the vaccinations, the lack of transparency will only fuel more conspiracy theories and drive people away from vaccination. Science by company press release isn't enough.
Spursex
Alert Team
I agree, but I also think we/The World has little choice but to get on with and accept that both these vaccines may well end up killing a few of us.
The NHS trusts delivering the injections now are set and ready to deal with the alleged anaphylactoid reactions that may or may not have been seen elsewhere.
So far, to my knowledge, no such reactions have been reported during this early roll-out.
Yep and another morbid thought is if the side effects are rare or only get picked up on long term studies, then those receiving the vaccine initially will be in the older age groups so you would imagine be unlikely to live long enough to be significantly impacted by it.
