A predictive algorithm to identify genes that discriminate individuals with fibromyalgia syndrome diagnosis from healthy controls, 2018, Saliqan et al

[Andy]

Objectives: Fibromyalgia syndrome (FMS) is a chronic and often debilitating condition that is characterized by persistent fatigue, pain, bowel abnormalities, and sleep disturbances. Currently, there are no definitive prognostic or diagnostic biomarkers for FMS. This study attempted to utilize a novel predictive algorithm to identify a group of genes whose differential expression discriminated individuals with FMS diagnosis from healthy controls.


Methods: Secondary analysis of gene expression data from 28 women with FMS and 19 age- and race-matched healthy women. Expression of discriminatory genes were identified using fold-change differential and Fisher’s ratio (FR). Discriminatory accuracy of the differential expression of these genes was determined using leave-one-out-cross-validation. Functional networks of the discriminating genes were described from the Ingenuity’s Knowledge Base.


Results: The small-scale signature contained 57 genes whose expressions were highly discriminatory of the FMS diagnosis. The combination of these high discriminatory genes with FR higher than 1.45 provided a leave-one-out-cross-validation accuracy for the FMS diagnosis of 85.11%. The discriminatory genes were associated with 3 canonical pathways: hepatic stellate cell activation, oxidative phosphorylation, and airway pathology related to COPD.


Conclusion: The discriminating genes, especially the 2 with the highest accuracy, are associated with mitochondrial function or oxidative phosphorylation and glutamate signaling. Further validation of the clinical utility of this finding is warranted.

Open access at https://www.dovepress.com/a-predict...ndividuals-peer-reviewed-fulltext-article-JPR

 

[mariovitali]

@Andy

cc : @ScottTriGuy @JaimeS


Making a correction / addition from other part of the text :

The top 3 canonical pathways that are associated with the discriminating genes are related to hepatic fibrosis/hepatic stellate cell activation, oxidative phosphorylation, and airway pathology in COPD (Figure 3).

and to be fair :

Follow-up studies are warranted to address several limitations of the study. There is a very high likelihood that the list of genes generated in this study maybe artifacts of over training on a single cohort of a small number of patients. For the findings to have clinical and diagnostic utilities, the predictive genes must be validated in a larger, independent cohort of patients with FMS. Further, future studies should account the overlap of FMS and ME/CFS diagnoses in the symptom presentation of study participants and for the presence of other medical comorbidities. In addition, the selected differentially expressed genes were obtained from raw microarray data, basing on our previous finding that using raw microarray data can better generate genetic signatures that are associated with functional pathways that are a priori known for specific medical conditions.39 Future studies should consider using preprocessing techniques, such as Robust Microarray Average, to determine if similar discriminatory genes can be identified.

 

[Adrian]

With such small amounts of data I'm not sure that any results will be meaningful. They use a cross validation techniques which is better than some we have seen.

 

[mariovitali]

With such small amounts of data I'm not sure that any results will be meaningful. They use a cross validation techniques which is better than some we have seen.

This is true and it’s been discussed in the text.

I think that we must see the bigger picture since we have from previous research work from Hanson, Naviaux , Flugge / Mella :

-Impaired Bile Acids metabolism
-Impaired phospholipid metabolism
-Metabolites suggesting hepatotoxicity
-Impaired Vitamin E metabolism which may be attributed to impaired hepatic function

All these may suggest that we must pay closer attention to the Liver

 

[Snow Leopard]

A previous report observed similar differential expressions of MRP and SLC genes in patients with chronic fatigue conditions (chronic fatigue syndrome, cancer, and HIV patients) compared to matched controls.

This is vaguely interesting - the question is are these directly involved in fatigue signalling mechanisms or are they merely a nonspecific side effect of different activity patterns of people who happen to be suffering from severe fatigue.

 

[mariovitali]

This is vaguely interesting - the question is are these directly involved in fatigue signalling mechanisms or are they merely a nonspecific side effect of different activity patterns of people who happen to be suffering from severe fatigue.

Good question.

For the record, the techniques that i use agree with other mentions in the paper for Protein Kinase B (PKB) and Nf-kΒ pathway.


In any case, i am really happy that these techniques are being put into use more and more. Used correctly, they may prove to be very useful in generating interesting hypotheses for ME/CFS.

 

[Amw66]

This is true and it’s been discussed in the text.

I think that we must see the bigger picture since we have from previous research work from Hanson, Naviaux , Flugge / Mella :

-Impaired Bile Acids metabolism
-Impaired phospholipid metabolism
-Metabolites suggesting hepatotoxicity
-Impaired Vitamin E metabolism which may be attributed to impaired hepatic function

All these may suggest that we must pay closer attention to the Liver

I agree, but virtually impossible to get anyone to consider this. I' ve given up with my GP and no private providers do any other investigative processes anywhere near us. I am hoping that this gets further study.

 

[mariovitali]

Just wanted also to add, as shown on the figure 4C of the paper below, although not a strong signal, Tyrosine is being mentioned :

I would like to confirm that based on the techniques i use, Tyrosine metabolism is an important element of ME/CFS (hypothesis). This was also discussed in the following post :



https://www.s4me.info/threads/machine-learning-assisted-research-on-me-cfs.5015/page-2#post-109782