Virginie’s first paper on her thesis work, “Network based meta-analysis prediction of microenvironmental relays involved in stemness of human embryonic stem cells” was published yesterday at PeerJ. She first put it up as a preprint (v1 here
revised v2 here and then submitted it – my first experience of this and something I will certainly do again.

At the heart of the paper is a simple question: “What is stemness?” The definition of an embryonic stem cell is that it can self-renew and form all parts of the body. So the question is central to our understanding of metazoan cell biology. To get to what could be termed a first level answer, Virginie performed a meta analysis of published transcriptome data. This highlights a major problem: we have few standards in biology and meta analyses are not straightforward. Indeed, some datasets are pretty much incompatible.
What we were particularly interested in was the relation between extracellular proteins, transcription and stemness. This is because the extracellular space and plasma membrane seem to be at the edge of the map in many analyses. Yet it is the extracellular proteins of metazoa that have changed the most and complexity of these proteins scale with organism complexity (excellent paper by Vogel and Chothia on the subject here).

Indeed, it is precisely the extracellular proteins that are manipulated in attempts to generate defined culture conditions for stem cell maintenance and their differentiation. Yet we lack systematic analyses of these proteins in the context of stemness.

As Virginie points out in the paper, using mRNA as a proxy for proteins is, of course, a major approximation. Nevertheless, the analyses demonstrate that beyond the outer surface of the embryonic stem cell plasma membrane lies a rich field, ready for picking. It is complicated, but then to expect that molecular phenomena that underlie fundamental biology to be simple is never going to happen. So the way is open to test some of these candidates to see whether the mRNA-based analyses do indeed identify extracellular proteins with a role in stemness and then it will be time for multidimensional proteomics – as beautifully described in different systems by Angus Lamond in the very stimulating seminar he delivered here on September 22.

I will end on subjects close to my heart.

My “natural” prejudice was that heparin-binding proteins might be particularly interesting and this looks to be true from Virginie’s data. So another angle to pursue is the large bull elephant that lurks in the small room of systems biology: glycosaminoglycans. These are not primary gene products so never figure in analyses of protein function.

Our catalogue of interactions is grossly incomplete. I think I am allowed to say this, as someone who has spent most of his career trying to measure protein-protein and protein polysaccharide interactions. Protein-protein interactions are catalogued according to “stringency”, a measure of the strength of the evidence for an interaction. However, we have to use these data on a ‘global’ basis. That is, experimental evidence for an interaction acquired in biological system A is assumed to hold true in biological system B. We have to make this assumption, because our coverage of molecular interactions is so very poor.

Open access and preprints. PeerJ was again an excellent experience and so was the preprint. Something I realised rather late in the day was that my use of supplementary information was entirely directed by the notion of print media: you put lots of stuff there to save paper. We caught this one at revision and re-organised the manuscript, so most of the data are in the paper. It makes sense and only a side story or “raw” annotated data for which there is no central data repository need go into supplementary.

Dear Dr Worms,
I write this letter in a personal capacity to express my views on the letter you sent to Dr Amaya Moro-Martin on behalf of the ESF, regarding her opinion piece in Nature. Note the word “opinion” and refer to Article 10 of the European Convention on Human Rights (on page 11, it is only two very short paragraphs) Continue Reading »

There are many prizes for cultural activities, of which science is one. This week has seen the announcement of the Nobel prizes, a little earlier the IgNobels were awarded. There are, of course many other prizes. I have decided to set up my own.
A question that bugs me and which loomed large while I read the excellent review by Ding Xu and Jeff Esko from UCSD on “Demystifying Heparan Sulfate–Protein Interactions” is how many extracellular proteins are there? Continue Reading »

A recent post at Retraction Watch revealed that Fazlul Sarkar of Wayne State University is behind the attempt to lift the anonymity of commenters at PubPeer
The Spectroscope has posted The REAL threat to PubPeer is a real threat to science communication.

I agree entirely. Continue Reading »

Dan Nieves’ paper on an easy and accessible method to covalently conjugate proteins, sugars and indeed pretty much any biomoleucle onto nanoparticles has just come out in Chem. Commun. Continue Reading »

On December 31 2013 I posted my New Year’s resolution: to only review manuscripts from open access or learned society journals.

My reasoning was that open access will only be the norm if we stop giving that which is most precious, our time, to closed access journals. I really think the wider community needs to start to be selective in reviewing. It is far easier to implement than the radical re-alignment of library journal subscriptions. Continue Reading »

This post is entirely inspired by a Tweet that appeared in my stream via @stuartcantrill, a request for ideas on the future of chemistry. My (instant) response was that we have to replace everything with materials derived from waste biomass. After finishing my morning check of information systems and my coffee, it was time to get on my bike and cycle to the university. This set off the lateral neuronal activity that my brain engages in when I cycle – the worse the traffic, the more lateral activity… Continue Reading »


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