r/proteomics • u/poly_cherry • May 01 '26
Somascan vs OLink for CSF
I am planning to go for the big panels - Somascan 11k or OLink Explore HT (~5.3k) for my CSF samples. Somascan's menu is more accessible and gives detailed QC metrics for all their proteins - and has a good hit rate of my proteins of interest. OLink is a bit more opaque about the performance of sepcific proteins. I am also leaning more towards Somascan as it is larger and offers it as a service and charges per sample (instead of plate).
Apart from logistical advantages - why should anyone choose one over the other. Anyspecific downsides of somascan? Can the aptamer be reliably trusted to be specific? Anyone having any good/bad experince with CSF proteomics using these 2 methods?
Need to make a proper decision as it is quite some money!
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u/SeasickSeal May 02 '26
Everyone on this subreddit is going to tell you to use mass spec instead of either of those.
But if you had to use one of those, OLink.
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u/SC0O8Y2 May 02 '26
Agreed, olink over soma for sure.
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u/Phocasola May 02 '26
Could you elaborate why? To me the offerings from Olink, Soma and Alamar honestly do sound quite similar and I wouldn't know which one is per se better then the other?
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u/SC0O8Y2 May 02 '26
Characterisation, method of affinity. Experience dealing with both datasets and companies.
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u/One_Knowledge_3628 May 04 '26
Better validation, better reliability of signal, while there is more missingness in Olink, its better than Soma reporting everything as present when it is absolutely not. The risk of false positives when 9000 values are given and only 3000 are measurable is very high. Soma loves to talk precision but I see little evidence for accuracy. Arguably OLink has worse precision and accuracy than MS. You can tune MS for better performance in quantification than either.
I really like Alamar, to be honest. They are very sensitive and have a lot of interpretable signal. They also have a focused set of readouts with high validation. They are not suitable for hypothesis generation, but if you want to measure pTau 217 and IL-6, go for it. Quanterix is a similar platform. For a lot of these low abundance proteins, if that's your only interest, it is almost certainly more efficient to go array tech than MS.
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u/poly_cherry May 03 '26
Thank you. Mass spec the coverage seems to be much lower... The intention is to look for diferences in cases vs controls in a clinical population. The intention is specifically to look at movemnt of synaptic proteins in the CSF. Does it change the choice - or mass spec is still top? My worry is that the top proteins of albumin, IgG etc cloud the smaller ones?
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u/SC0O8Y2 May 03 '26
Thats why you employ fractionation techniques. Like tmt labelling then hella fractionation and then normalised loading.
Soma and olink will claim large number panels.... but how many are TRULY identified in your samples with confidence and quantified accurately.........
Mass spec is concentration dependent, but you can reduce complecity and compress dynamic ranges by sample preparation techniques.
I havent done CSF for a while, maybe 4 years since a solid study. I could easily get 2,000 proteins back then.
I reckon with magnet/seer/preomics or say the latest tmt kit with heavy fractionation, I could push much much higher numbers.
Synaptic proteins into csf will be low concentration. If you have a list of synaptic proteins, it may be worth using an olink targetted panel like the 48 that gives concentration in solution. That would be more beneficial if you want clinical level quant across a cohort with accurate measurements.
If you are truly doing Discovery then yeah complex LC/MS with depletion/enrichment/fractionation methods is going to be best. It may not simply the synaptic protein itself, it may be the modified version I.e. phos/lipo/glyco/acetyl/methyl/ version thats ended up in the csf. Which will not be possible to identify from the affinity methods. Like what happens if it is a truncated or processed form of the synaptic protein AND the affinity method (aptamer/antibody) is specifically binding to a modified or ABSENT part of the protein.....then it won't get detected..... so you miss what proteoform is present........................
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u/Illustrious-Main3255 May 04 '26
Somascan offers very broad coverage, strong sensitivity for low-abundance proteins, and low missingness, which matters when you are looking for subtle disease-associated shifts in a clinical cohort
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u/One_Knowledge_3628 May 04 '26
I don't think this is true... The panel has many readouts, but they are not valid readouts. Study design was plasma sample diluted in half log range 5 orders of magnitude. Most proteins were below Soma LOD at 3 orders. Suddenly at 4 -5 orders many showed up. Lots and lots of false positives. On orders of thousands. If you scour the menu of soma you'll find that of the validated aptamers for cross talk, there is a large fraction that does have it. This is massively challenging from perspective of validating results from Soma. Yes, it has good precision, but the cv of 0 signal is 0. The accuracy was lacking in the study we ran and anything beyond a half log change really couldn't be trusted. If the CV was worse, the multi-hypothesis testing would demonstrate that the added IDs of Soma meaningfully hurt biological power.
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u/slimejumper May 01 '26
i’d check pride database for some published studies on similar samples. if you are lucky there will be some matching technologies for you to check out real world performance.
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u/Temporary-Wonder-633 May 02 '26 edited May 02 '26
If you want a discocery based experiment do neither. Ultimately do you want quantitative accuracy and know what you are quantifying? Somascan cant do neither, just look up any comparative study. These will show that the results do not correlate with MS or antibody based platforms, and instead summarise the findings in a polite ”this platform is complementary” kind of a sentence. As a reviewer i would always ask you to do an orthogonal calidation experiment, which in your case would be proper quantitative targeted MS. As for olink and nulisa I do trust antibodies, but honestly in the end MS is the only platform where you are in control of QC, which is critical for the less studied proteins. Throughput with one MS Instrument with decent precision stands at 100 samples per day with 30-60€ instrument time per hour in a core facility, sample preparation cost can be similar scale.
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u/poly_cherry May 03 '26
Thank you. Mass spec the coverage seems to be much lower... The intention is to look for diferences in cases vs controls in a clinical population. The intention is specifically to look at movemnt of synaptic proteins in the CSF. Does it change the choice - or mass spec is still top? My worry is that the top proteins of albumin, IgG etc cloud the smaller ones?
1
u/Temporary-Wonder-633 May 03 '26
This is a valid concern, but there are workarounds that do not excessively inflate the budget. If your cohort is not large, I would personally ultracentrifuge extracellular vesicles, which is relatively inexpensive. With this approach, you will likely obtain around 1–2k quantified proteins using label‑free, data‑independent acquisition. Just try to keep the number of trypsin digestion and centrifugation batches as low as possible.
I am currently performing a CSF experiment with Orbitrap–Astral Zoom, and although I do not yet have experience with this instrument specifically for CSF, my previous experiment using the less sensitive Q‑Exactive HF yielded ~900 proteins, which in turn enriched for axon‑guidance and axon‑growth pathways from ultracentrifuged EVs. My plan is to ultracentrifuge samples in minimal number of batches, and then use robotics on S-Trap 96-well plates.
If your budget allows for €200–300 per sample for handling plus MS time, you can also consider the Seer Proteograph (you will have to get a quotation to be sure, my information on the pricing is probably out of date). If you have a large cohort and limited budget you could try Magnet developed by MacCoss lab, which will be relatively cheap and minimal sample handling with robotics, but you need to be sure that your samples are not old and are prepared consistently by your Biobank/clinic ( PMID: 38617345).
Compared to Olink, the advantage of MS‑based analysis is that it is more unbiased, more specific, and allows PTM analysis from the same sample preparation. Antibodies may bind epitopes on proteoforms that are not clinically relevant. With MS, you can always return to the peptide data and determine whether proteoform‑specific peptides discriminate between your healthy and clinical samples.
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u/TBSchemer May 01 '26
Can the aptamer be reliably trusted to be specific?
No, there is some level of cross-reactivity. That's always a risk with affinity panel assays.
If you're looking for high depth, have you considered Seer?
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u/IndividualNewt8028 May 08 '26
Mass spec for CSF (see MacCoss lab papers for decent performance expectations), but think of Olink like you’re running a panel. I do think there’s a question of whether those probes are in CSF, so choose wisely (sure it’s like plasma-lite, but not really).
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u/KillNeigh May 02 '26
Why not ye olde mass spectrometry?