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The Twelve Days of Biomarkers (2023/12/19)
Winny, the Proteomics Ontology & Oncology Predictor, is a novel algorithm for discovering biomarker-like proteins. It requires a good quality MS/MS data set for the cancer/cell-type of interest & access to GPMDB. The examples below were all obtained using GPM06610049332, a multidimensional chromatography data set from Johansson, et al. (PubMed). Winny works just as well on data from samples treated with reagents for the purposes of relative quantitation, e.g., iTRAQ or SILAC, as it does using untreated samples.

The sort of thing people want to find in a biomarker experiment, but very rarely do.

:p (cytochrome P450 family 4 subfamily Z member 1): Human Protein Atlas mRNA tissue distributions & GPMDB protein tissue & cancer tabbulations.

From the final exam for "Biomarkers: fact & fiction".

This protein has potential as an indicator of breast cancer. Describe how you would go about verifying its clinical utility. Be sure to include estimated duration & cost of the necessary studies.

:p (glial cell line-derived neurotrophic factor family receptor alpha 1): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulations.

From the final exam for "Biomarkers: fact & fiction".

This protein has potential as an indicator of breast cancer. Describe how you would go about determining if it is best suited to be a marker for primary (at the site of origination) or secondary (metastatic, disseminated) tumour tissue.

:p (C-type lectin domain family 3 member A): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulations.

From the final exam for "Biomarkers: fact & fiction".

This protein has potential as an indicator of a tissue specific adenocarcinoma. Discuss the case for and against using of an intracellular metabolic enzyme for this purpose.

:p (glycine-N-acyltransferase like 2): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

This protein has potential as an indicator of two tissue specific adenocarcinomas. What additional clinical information would be necessary to distinguish between these alternatives given a positive test for the protein?

:p (gastrin releasing peptide receptor): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

This protein is elevated in invasive ductal carcinoma, compared to other cancers. Discuss research on using ESR1:p & its sequence features to clinically classify breast cancer tumours and its use in selecting treatment option.

:p (estrogen receptor 1): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

The mRNA & protein associated with this gene are both elevated in breast cancer. Discuss the pro & cons of using either (or both) of these molecules in clinical diagnosis. What types of lab tests would be required for each modality & how you would go about determining diagnostic interpretations for the results?

:p (mucin like 1): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

The mRNA & protein associated with this gene are both elevated in breast cancer. Use this protein as an example of how to utilize absolute protein levels in tumours both for the purposes of sub-typing the disease and guiding treatment.

:p (progesterone receptor): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

This protein converts norepinephrine (noradrenaline) to epinephrine (adrenaline) and is found to be elevated in some breast cancers. Discuss how you would validate using this protein as part of a multi-protein prognostic signature for clinically relevant tumour types.

:p (phenylethanolamine N-methyltransferase): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

This cell surface peptide hormome receptor has a well-understood function in normal breast tissue & its dysfunction is involved in tumour proliferation. List & discuss three cytokine-associated transcription pathways that can be affected by the prolactin/PRLR:p complex.

:p (prolactin receptor): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

This rarely observed, apoptosis-related protein is over-represented in breast cancer tissue. Discuss the pros and cons of using a protein involved in a cell death process as a diagnostic marker in clinical test.

:p (pyrin domain containing 1 ): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation.

From the final exam for "Biomarkers: fact & fiction".

This gene, also known as mammaglobin-1, shows significant protein & mRNA enrichment in invasive ductal carcinoma. Describe three practical analytical methods of using this observation to create a clinical test to positively identify breast cancer metastatic lesions.

:p (secretoglobin family 2A member 2): Human Protein Atlas mRNA cancer type distribution and GPMDB cancer type tabbulation. (12/12, fin)

Mainly melanoma (2023/12/19)

Melanoma has so many unique protein markers it must make the other cancers jealous.

PMEL (premelanosome protein): Human Protein Atlas mRNA cancer type distributions & GPMDB protein cancer type tabbulations.

Melanoma is a cornucopia of cancer-specific protein biomarkers. Makes me wonder why CPTAC hasn't put any effort into it yet.

(tyrosinase-related protein 1): Human Protein Atlas mRNA cancer-type distribution and GPMDB protein cancer-type tabbulations.

Another day, another melanoma biomarker.

(tyrosinase): Human Protein Atlas mRNA cancer-type distribution and GPMDB protein cancer-type tabbulation.

Another day, another melanoma biomarker.

(tyrosinase): Human Protein Atlas mRNA cancer-type distribution and GPMDB protein cancer-type tabbulation.

This one is a membrane protein with 11 TMs, normally found at low levels in melanocytes but more prominent in melanoma.

(solute carrier family 24 member 5): Human Protein Atlas mRNA cancer type distribution and GPMDB protein tissue & cancer type tabbulations.

It seems to work. An eigenvalue here, an eigenvalue there, some stats, some nice data, a lot of information & bingo-bango-boom, there they are.

:p (OCA2 melanosomal transmembrane protein), :p (baculoviral IAP repeat containing 7), :p (melan-A), :p (dopachrome tautomerase): Human Protein Atlas mRNA cancer type distribution and GPMDB protein tissue & cancer type tabbulations.

RPS4Y1: it's a boy! (2023/12/17)

From the final exam for "Biomarkers: fact & fiction".

If you had MS proteomics data from a solid tumour & you wanted to know if it was from a male or a female donor, which gene/s would be best to use to make that determination:

Thanks to everyone who participated.
SRY is the only Y-chromosome only gene, but it isn't observed in experiments.
The combination of AMELX:p & AMELY:p is observed & has been used to successfully determine the sex of archeological samples, but they are only present in tooth enamel.

The most abundant, suitable Y-chromosome protein in normal tissue is RPS4Y1:p (ribosomal protein S4 Y-linked 1), found everywhere there are ribosomes. The protein has 3 frequently observed tryptic peptides not present in the X-linked version RPS4X:p:

(156–168) k . VNDTVQIDLGTGK . i
(175–191) k . FDTGNLCMVIGGANLGR . v
(222–240) r . LSNIFVIGNGNKPWISLPR . g

NEBL: a tale of two splices (2023/12/7)

This protein is used by cardiac muscle sarcomeres the same way that skeletal muscle sacromeres use the much larger nebulin (hence the diminutive "-ette" in its name).

(nebulette): Human Protein Atlas mRNA tissue distribution & GPMDB protein tissue tabbulations.

Good story, but what is it doing in brain, breast & kidney then. They don't have any sacromeres or similar structures. Looking a little closer, the coverage diagram for the top 20 observations of NEBL:p in heart shows about what you would expect.

The same diagram for the top 20 observations in non-cardiac tissue show something different (brain & prostate shown).

It turns out that there is a short splice variant that is made up of a few of the back end exons from the longer form, plus a few additional exons that make up the short protein's N-terminus. This shorter alternate form is referred to as LIM-nebulette and it is the most commonly observed splice variant derived from the gene NEBL:g (coverage for LIM-nebulette observed in brain).

A coverage diagram of LIM-nebulette observed in heart muscle shows strong signals from the shared exons corresponding to the longer splice, with a scattering of less intense signals from the exons unique to the LIM splice, showing that the short form is present too, but to a lesser extent.

Solute carrier proteins you are likely to find in human urine, but rarely anywhere else–other than kidney (2023/12/01)
  1. SLC1A1
  2. SLC2A5
  3. SLC3A1
  4. SLC5A1
  5. SLC5A2
  6. SLC5A8
  7. SLC5A9
  8. SLC5A10
  9. SLC5A12
  10. SLC6A19
  11. SLC12A1
  12. SLC13A2
  13. SLC13A3
  14. SLC17A3
  15. SLC22A2
  16. SLC22A4
  17. SLC22A5
  18. SLC22A6
  19. SLC22A11
  20. SLC22A12
  21. SLC22A13
  22. SLC23A1
  23. SLC26A4
  24. SLC28A1
  25. SLC34A1
  26. SLC36A2
  27. SLC44A4
  28. SLC47A1
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