Here, we discuss the use of WIMG tools to search for drugs or treatments or gene perturbations that may reverse various disease signatures. Perhaps I'm jumping the gun a bit here...it would first be nice to show that reversing a disease signature can actually reverse a disease. I may provide concrete examples that both confirm and contradict the possibility in the future. Based on the experience of scouring tens of thousands of studies, however, it is fairly obvious that reversing a disease signature can often, if not always, effectively treat a disease. When examining cancer signatures, for example, MEK inhibitors, commonly used in cancer treatment, often do a fine job of downregulating transcripts that are upregulated in cancer, and upregulating transcripts that are downregulated in cancer. We will ignore complicating factors such as resistance. We also assume that readers are educated/experienced enough to understand that most treatments involve tradeoffs...self-experimentation is not recommended.
We've accumulated a number of gene lists involving "canonical" disease signatures. They are listed at the bottom of this page. Additional details, such as the number of studies examined in accumulating the data, are omitted for simplicity. If your disease of interest is found in the list below, you can perform several actions to search for studies in which the signature is reversed. For example, you could open up the "Fisher" app, enter the DBASE ID for "WIMG up-regulated in bald skin" in the "Enter identifers or database ID" box, and simply hit "submit." If you are only interested in reversing the signature, select "downregulated" in the "Regulation" box. Then again, if you're interested in searching for factors that could encourage balding, you could choose "upregulated." You can also enter both portions of a study (upregulated and downregulated) into the "Match Studies" tool; to reverse the two be sure to select "Inverse Correlations." It is advisable to try both apps, if possible: "Match Studies" will give you individual studies ranked according their potencies in reversing both the up- and down-regulated portions of a study. It's possible that the most potent treatment for disease reversal would involve separately altering the up- and downregulated portions (i.e. two drugs), in which case you'd want to stick with the Fisher app.
If you're only interested in drug-based treatments, you can choose "drug" in the "Experiment" box. Choose "treatment" for non-small-molecule approaches (antibody-based therapy, etc). "Environment/behavior" might also be worth examining.
One nice, very unique WIMG option is the "natural" option in the "Cell Type" box*. Choose it, and you will only receive "do-it-yourself" types of treatments as output...fitness programs, diets, vitamins, Chinese medicine, and stuff you might find in a "health-food" store. Again, I will assume readers are mature enough to be cautious here.
It is possible that the upregulated (or downregulated) portion of a disease signature would best be reversed by two or more treatments. Here, you might consider using the "Third Set" tool. Enter, say, the upregulated portion of disease transcripts and the downregulated portion of a signature involving a drug that you know to be effective. It's important that "Set1" be the upregulated disease signature. The tool will spit out a list of studies that intersect with the disease signature, but not the known drug signature.Again, you will probably wish to select "downregulated" in the "Regulation" box, and something like "drug" in the "Experiment" box. If you're insane and wish to find three non-overlapping drug treatments, you'll need to know all the transcripts that are considered to be downregulated in the two drug studies above...WIMG doesn't provide you with this, so you could contact us or dig up that data yourself in the studies of interest. Find the union of those two sets and discard one copy of any genes that appear twice. Use this new "dual" drug signature in the "Match Studies" tool, along with the upregulated disease signature.
Looking below, you will see that we have a fairly limited selection of canonical disease signatures to choose from. That's because we usually create these lists when there's a substantial selection of studies from which we can draw repeatedly perturbed genes. If you wish to reverse a disease signature that doesn't have a "WIMG list", you can create one yourself using whatever studies you can find. In the case of a rare disease, there may be only one study that is relevant. It's possible that no studies exist for a disease of interest, in which case you would have to find a signature for a similar disease. You could ask us to try to dig up the studies...don't worry, we're neurotic about hoarding and analyzing data.
DBASE ID STUDY
118765101 WIMG canonical up in cancer vs. adjacent
118766101 WIMG canonical down in cancer vs. adjacent
118767101 WIMG canonical up-regulated in metastasis vs. primary
118768101 WIMG canonical down-regulated in metastasis vs. primary
118771101 WIMG new canonical cytokine storm up
118772101 WIMG new canonical cytokine storm down
123049121 WIMG canonical up in human Alzheimer's brain
123050121 WIMG canonical down in human Alzheimer's brain
123069121 WIMG canonically upregulated in blood of Alzheimer's patients
123070121 WIMG canonically downregulated in blood of Alzheimer's patients
124415121 WIMG canonically up in Parkinson's brain
124416121 WIMG canonically down in Parkinson's brain
124416122 WIMG canonically down in alcoholic brain
124416131 WIMG canonically up in alcoholic brain
124417121 WIMG canonically up in schizophrenia brain
124418121 WIMG canonically down in schizophrenia brain
124419121 WIMG canonically up in depression/bipolar brain
124419122 WIMG canonically down in depression/bipolar brain
124420121 WIMG canonically up in autism brain
124421121 WIMG canonically down in autism brain
125583121 WIMG canonical up-regulated in aging brain
125584121 WIMG canonical down-regulated in aging brain
137716203 WIMG canonically up-regulated in lung squamous cell carcinoma vs lung adenocarcinoma
137717203 WIMG canonically down-regulated in lung squamous cell carcinoma vs lung adenocarcinoma
141048203 WIMG canonically up-regulated in lung cancer
141049203 WIMG canonically down-regulated in lung cancer
141259203 WIMG up-regulated in liver cancer vs adjacent
141260203 WIMG down-regulated in liver cancer vs adjacent
142124203 WIMG canonically up-regulated in colorectal cancer vs adjacent/normal
142125203 WIMG canonically down-regulated in colorectal cancer vs adjacent/normal
142928203 WIMG up-regulated in cervical cancer
142929203 WIMG down-regulated in cervical cancer
143176203 WIMG transcripts rarely perturbed in human cancer
143177203 WIMG transcripts most commonly perturbed in human cancer
143178203 WIMG transcripts most rarely up-regulated in human cancer
143179203 WIMG transcripts most commonly up-regulated in human cancer
143180203 WIMG transcripts most rarely down-regulated in human cancer
143181203 WIMG transcripts most commonly down-regulated in human cancer
146502203 WIMG genes that are rarely down-regulated in cancer vs adjacent studies
146503204 WIMG genes that are rarely up-regulated in cancer vs adjacent studies
146503205 WIMG genes that are never down-regulated in our cancer vs adjacent studies
146504206 WIMG genes that are never up-regulated in our cancer vs adjacent studies
160517531 WIMG up-regulated in aging
160518531 WIMG down-regulated in aging
160519531 WIMG up-regulated in HUMAN aging
160520531 WIMG down-regulated in HUMAN aging
164739532 WIMG up-regulated in bald skin
164740532 WIMG down-regulated in bald skin
165959532 WIMG up-regulated on cancer recurrence
165960532 WIMG down-regulated on cancer recurrence
165961532 WIMG up-regulated in high vs low-grade cancer
165962532 WIMG down-regulated in high vs low-grade cancer
176813532 WIMG up-regulated in blood of systemic sclerosis patients
176814532 WIMG down-regulated in blood of systemic sclerosis patients
180119532 WIMG up-regulated in inflammatory disease
180120532 WIMG down-regulated in inflammatory disease
*Why is the "natural" option found in the "Cell Type" box? It's unintuitive, but it was easy to program. We can fix that in the future.
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