Application for RAMSAY Awards 2019 - Machine Learning-assisted Research on ME/CFS

Dear All,

I wanted to inform you about my application to SolveCFS for a RAMSAY award funding and the final decision. The title of the application was :

"The use of artificial intelligence and network analysis methods to identify mechanism(s) responsible for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome"


I present the introductory text :

The application was scored by two reviewers for Significance, Innovation, Approach and Overall Impact. I believe that it is not right to share the comments of the two reviewers. They were invaluable in making me understand the pros and cons of the solution that was built over the past 6 years and the difficulties i had in communicating the capabilities of this framework.

Waiting for the "verdict" was a painstaking process (the application was submitted in July). After all, i waited for this moment since 2013.

I was informed yesterday that the application was not successful. I do not -by any means- wish to criticise this decision. I did not have the opportunity to "defend" my application with the reviewers but i do understand that this process may not be applicable. The news took a toll on me. I was prepared for a negative outcome but i also had positive thoughts. Creating such framework was not easy. I had to work very hard and this effort had several negative repercussions on my personal life and also financially-wise as i had to work for many - many hours.

I thought that the right thing to do is to finally give up and move on with my life. I then reminded myself that i am symptom-free because i didn't give up and instead persisted in finding a solution for me.

As i mentioned in older posts, the great thing about forums is that they leave a written record of whatever is being said. Here are my takeaways :

- I would like to particularly Thank @ScottTriGuy for his help and tremendous effort to make this work heard. Also Jane, @wigglethemouse and @Ben H .

-I stand strong in believing that AI will be a game-changer for putting the pieces of the puzzle together

-I will do anything possible to have results of this work being used by other researchers helping them to better understand the bigger picture. I have ready specific blood tests, compounds and also identified potential sub-problems (e.g Cysteine catabolism, Glutamate metabolism) that may be responsible for the perfect storm we are seeing. Unfortunately under these circumstances this task will not be easy.

I will never quit. Ever. Until we find a solution.



Stay strong,

"Mario"

 

Sorry to hear you weren't successful this time Mario, glad to hear though that you intend to persist in your efforts.

 

Thanks for your efforts Mario,

 

@Trish , Thank you so much.

I was hoping to do that, being under different circumstances (in case that the award was given) as this would have made researchers more receptive. SolveCFS may help me in contacting research labs and if such thing takes place, it would be a great start.

There are many things to share . SolveCFS will be providing a mobile application for ME patients to track their symptoms. Through the CureME team, i managed to inform SolveCFS that i did the same kind of tracking in 2011 and shared with them some Best practices plus some thoughts on having people continually use the application. One of the most difficult parts in keeping a log ( i had to do this for 434 days) was not giving up but continuing each and every day to log symptoms.

Certain insights were extracted such as being on a fat-free diet induced my symptoms (wasn't aware of that) and how gluten would induce brain fog (which i kind of knew). The other amazing thing i noticed was how weather variations induced my symptoms with greater being humidity. I had to use specialised hardware to receive data as these changes were happening :

https://forums.phoenixrising.me/threads/me-better-when-abroad.53988/#post-897595

My hypothesis is that high humidity makes worse the inflammatory response that takes place. I strongly believe that inflammation is a key aspect for many ME patients and their symptoms.

 

I'd just like to echo the comments above, particularly Trish's. Thank you for your persistence and I'm very pleased that you are healthy and intend to continue your efforts.
The whole experience is understandably personal for you and yet you seem to have maintained your objectivity. Not easy by any means. I tip my hat to you.

 

Agreed, there are inherent problems. Keeping in mind that the data originates from PUBMED abstracts we also have issues such as publication bias. I decided to go ahead and build the system despite these issues and see what would come out and whether findings make sense.

Since you appear to have knowledge about these technologies, here is a short description :

a) For text analysis, Information Extraction and Natural Language Processing are used
b) matched medical entities are transformed to a numerical representation, suitable for further analysis
c) Machine Learning algorithms then try to identify which medical entities are associated with the cluster of symptoms we are finding to ME/CFS. The libraries/software used is SCIKIT-Learn, WEKA, R,KNIME, H2O and others.
d) Network Analysis attempts to find entities, central to ME/CFS-related topics

 

@mariovitali Have you come across any API's or tools to extract historical weather data from the internet? I'd love to track data because like you I've noticed a correlation but have no data to back it up.

 

I never used an API but have been using wunderground. Here is an example :

https://www.wunderground.com/history/weekly/gr/spata/LGAV/date/2019-10-8

To be sure about the effects of weather on my self, i had to buy hardware. So i ended up installing a Kestrel 5000 series weather station at my balcony which measures wind direction, humidity, temperature and many others. it was important to track weather changes as they happened.

https://kestrelmeters.com/

This was a very cool setup. I had the weather station connected to my cell phone through bluetooth and could see the immediate consequences that wind gusts had on the pain i was experiencing or other symptoms.

cc : @Perrier

Here are some notes from how my body responded.Please keep in mind that these notes are applicable to me but you may find that the patterns also apply to you :

As discussed, i understood that tinnitus was a key aspect of my symptoms. I later understood that tinnitus signified a "crash" (and was part of my vicious cycle)

1) I realised that tinnitus would happen before major weather changes : Humidity, wind speed, temperature drop
2) Symptoms would be more intense with combined changes. Example : High humidity weather and high south winds. North winds were better vs South winds
3) Especially when the weather was humid, i could feel the pain on active sites of inflammation (e.g my periodontitis and certain points where the problem is bigger). Also my liver area and spleen.
4) Ideal weather conditions associated with far less symptoms : No wind, no rain, humidity at around 50%. Places with high weather variability would be the hardest ones for me (e.g the UK )

This was very important information because i was able to have a feedback mechanism to optimise my regimen. So using the weather station i would see -given weather conditions- how many symptoms i was experiencing. If my symptoms would be less on a high humidity day then that meant that my current regimen was doing something beneficial.

Then we have the connection with food. I knew that some foods would also immediately induce tinnitus :

-Whey protein
-Parmesan cheese
-Protein Bars

The common factor of these is high glutamate content. Another thing i am looking at is foods with high Polyamine content :

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022763/

I am not sure about this yet, but i believe that high content of polyamines may not be beneficial. It's been identified algorithmically but -as discussed- the algorithms do not tell us if what is identified is good or bad for our symptoms. My hypothesis is that Polyamines are important because their connection with Diamine Oxidase (DAO) functioning and GABA production but i need to work more on this.

Glutamate is excitotoxic. This is why i would be very interested to know @Andy what Dr Van Elzakker has to say about this. Can we find excitotoxic lesions anywhere? Can we measure it in vivo?

 

We did discuss glutamate and glutamine but I'm afraid we didn't get to those specific questions, not enough time for all the questions suggested.

He did suggest that we might do another video at some point, so I may well get the chance to address the questions that I didn't ask then, or if you didn't want to wait for that then perhaps contact him direct?

 

This might be just my impression, but he was not very receptive to my tweets mentioning him. I think it would be better for someone else to get in contact with him just to be on the safe side.

 

@Andy

cc : @Perrier , @wigglethemouse

I believe this should be one more interesting question for Dr Van Elzakker. Vitamin K metabolism which has been identified through Network Analysis since 2017 :

Is it possible that problematic functioning of genes related to Vitamin K metabolism affect glutamate modification / catabolism? Could a perfect storm be a combination of Vitamin K-dependent functioning along with other problematic genes responsible for Glutamate metabolism/catabolism such as GAD1, DAOA ?

Note that warfarin affects Vitamin K absorption (snapshot from SolveCFS website, slide from my presentation at EUROMENE) :







Network Analysis, generated in 2017 :







Perhaps i should have written "glutamate catabolism" below instead of "apoptotic cell clearance impairement". Note also that the 3 SNPs of this severely ill patient have to do with warfarin response.

 

@mariovitali - It is so frustrating trying to get funding for ME research, and the Ramsay awards seemed like such a good fit - no doubt it is discouraging not receiving funding, especially when so many patients are suffering and so much research needs to be done - since there is so little funding available generally, I imagine there were a lot of applications competing.

It takes grounded wisdom to able to put everything - including your considerable time, energy, money - into the larger context and take away feedback from the reviewers as learning to take forward, that speaks to your openness, resilience and commitment to the cause.

Thanks for continuing to push your research forward, in spite of the seemingly Sisyphean up hill path, because what you've uncovered and your self-experiments and your recovery, have great value that needs to be delved into deeper. Sooner than later.