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Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome With Partial Least Squares Discriminant Analysis: Relevanc... (González-Cebrián, 2022)

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Diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome With Partial Least Squares Discriminant Analysis: Relevance of Blood Extracellular Vesicles
(González-Cebrián, 2022)


Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a chronic disease characterized by long-lasting persistent debilitating widespread fatigue and post-exertional malaise, remains diagnosed by clinical criteria. Our group and others have identified differentially expressed miRNA profiles in the blood of patients. However, their diagnostic power individually or in combinations seems limited. A Partial Least Squares-Discriminant Analysis (PLS-DA) model initially based on 817 variables: two demographic, 34 blood analytic, 136 PBMC miRNAs, 639 Extracellular Vesicle (EV) miRNAs, and six EV features, selected an optimal number of five components, and a subset of 32 regressors showing statistically significant discriminant power. The presence of four EV-features (size and z-values of EVs prepared with or without proteinase K treatment) among the 32 regressors, suggested that blood vesicles carry relevant disease information. To further explore the features of ME/CFS EVs, we subjected them to Raman micro-spectroscopic analysis, identifying carotenoid peaks as ME/CFS fingerprints, possibly due to erythrocyte deficiencies. Although PLS-DA analysis showed limited capacity of Raman fingerprints for diagnosis (AUC = 0.7067), Raman data served to refine the number of PBMC miRNAs from our previous model still ensuring a perfect classification of subjects (AUC=1). Further investigations to evaluate model performance in extended cohorts of patients, to identify the precise ME/CFS EV components detected by Raman and to reveal their functional significance in the disease are warranted.



The study: https://www.frontiersin.org/articles/10.3389/fmed.2022.842991/full
 

Wishful

Senior Member
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It's an interesting approach. I do think that ME's core dysfunction is something hiding in EVs in a limited portion of the brain, and that finding it will take this sort of approach.

The flaw I see in their research is the use of healthy controls. For comparison with severe ME patients, the controls should also be bedridden or otherwise limited in physical activities. Otherwise they might only be 100% accurate in distinguishing bedridden patients from healthy active ones.
 

pattismith

Senior Member
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To further explore the features of ME/CFS EVs, we subjected them to Raman micro-spectroscopic analysis, identifying carotenoid peaks as ME/CFS fingerprints, possibly due to erythrocyte deficiencies.

I'm not sure I understand this well...
 

Rufous McKinney

Senior Member
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13,467
For comparison with severe ME patients, the controls should also be bedridden or otherwise limited in physical activities.

agree healthy controls is a concern.

but people not exercising or bedridden have their reasons thats occurring. which complicates any result, also. And its probably not A reason but numerous ones.

Its a perplexing challenge. Rather a stumper..I will keep pondering,
 

pattismith

Senior Member
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A few quotes from the discussion section:

It is worth mentioning that among the blood analytic group of variables the iterative PLS-DA modeling process selected, blood creatine phosphokinase (CK, labeled as cpkbloodb, please see Supplementary Table 1 key tab for variable nomenclature used) level was a feature retrieved with and without the inclusion of Raman data

Highly expressed in muscle, heart, and brain the CK enzyme holds a key role in ATP homeostasis.


@pattismith maybe of interest, for further context search for the below passages in the paper.
[...] it is interesting to observe that increased mean corpuscular hemoglobin (mch) and mean corpuscular hemoglobin concentration (mchc), which have been related to decreased deformability of RBCs (61), were identified by our PLS-DA analysis as variables with high discriminant diagnosis capacity (Figure 6; Supplementary Table 1). It seems relevant to mention that Fiedor et al., have recently shown that increased beta-carotene concentration in RBC membranes affect cell's shape, sensitivity to osmolysis and alters hemoglobin-oxygen affinity with potential physiologic implications (62).
 

Pyrrhus

Senior Member
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Location
U.S., Earth
increased mean corpuscular hemoglobin (mch) and mean corpuscular hemoglobin concentration (mchc), which have been related to decreased deformability of RBCs (61), were identified by our PLS-DA analysis as variables with high discriminant diagnosis capacity

For many years, increased mean corpuscular hemoglobin (MCH) and increased mean corpuscular volume (MCV) have been the only consistent abnormalities in my complete blood count (CBC) test.

I have always chalked it up to some micronutrient deficiency impairing maturation of erythrocyte precursor cells, since red blood cells with high hemoglobin content and larger volume are generally old red blood cells whereas young red blood cells tend to have lower hemoglobin content and smaller volume.

But there may be other explanations, of course...
 
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Wishful

Senior Member
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5,862
Location
Alberta
but people not exercising or bedridden have their reasons thats occurring. which complicates any result, also.

One benefit of the computer age is that researchers should be able to use data from other studies. There should be a lot of data from patients in various states, such as bedridden, so if they could tap into those studies they should be able to find common factors that can be filtered out. It's complicated by legal issues and data ownership and a lack of standards for how data is compiled and so forth, but eventually this should be a useful technique for research.
 
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