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\begin{document}

\title{Cross Country Collaboration To Better Map Human Kinase Regulation}


\author[ ]{Josh Nicholson}

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\date{}

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Dr. David Ochoa is a Postdoc
in~\href{http://www.ebi.ac.uk/research/beltrao}{Pedro Beltrao's lab} at
\href{http://www.ebi.ac.uk}{EMBL-EBI}~studying human kinase regulation,
one of our cells most active mechanisms for controlling cellular
behavior. ~Ochoa discusses with us why he performed this research and
how it was accomplished, a collaboration across three different
countries and labs. ~He highlights the significance of his findings and
and why he choose Authorea to write up his research. ~You can read more
about David's work
\href{https://www.ebi.ac.uk/about/people/david-ochoa}{here}.\selectlanguage{english}
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\par\null

\section*{\texorpdfstring{You're the first author on ``An atlas of human
kinase regulation'' \cite{Ochoa_2016}.~ This seems like a massive
research effort to catalog kinase regulation. What lead to the idea and
how did you accomplish the
research?}{You're the first author on An atlas of human kinase regulation \cite{Ochoa_2016}.~ This seems like a massive research effort to catalog kinase regulation. What lead to the idea and how did you accomplish the research?}}\label{youre-the-first-author-on-an-atlas-of-human-kinase-regulation-citeplaceholder1id.-this-seems-like-a-massive-research-effort-to-catalog-kinase-regulation.-what-lead-to-the-idea-and-how-did-you-accomplish-the-research}

\par\null

The idea behind this project was to learn how human cells elaborate
decisions and ultimately trigger responses that make them adaptable to
changing environments. One of the fastest mechanisms by which cells can
modulate their internal processes is kinase regulation. Kinases are
enzymatic proteins capable of governing cascades of events happening
inside the cells within a few seconds. In fact, deregulation of kinases
is very often associated with cancer and disease. However, our
understanding of kinase regulation has always been limited to the
simultaneous study of a few kinases. In this project, we have collected
42 parallel mass spectrometry studies quantifying close to 3 million
events. By crowdsourcing all this data from the community, we were able
for the first time to have a general view of how half of the known
kinases take coordinated decisions across a large panel of
perturbations.

\par\null

\section*{What was the key finding of the paper? Where there any
surprises along the
way?}\label{what-was-the-key-finding-of-the-paper-where-there-any-surprises-along-the-way}

\par\null

One of the most relevant findings is the indication that kinase
regulation profiles can be used as a barcode to distinguish specific
responses occurring in human cells. In other words, if we perturbed the
cellular environment in a similar way, the same specific pattern of
responses is activated inside the cells. The profiling of the kinase
regulatory status opens multiple possibilities. For instance, someone
can start wondering which drugs activate a similar pattern of kinases as
an already approved drug. Instead, someone might also try to revert or
engineer different internal processes keeping track of the resulting
kinase activation barcode.

\par\null

Additionally, we also discovered that the profile of kinase regulation
across perturbations is useful to search for other molecules that might
be responsible for the cellular response. This indicates a fundamental
link between who takes the decisions and who executes them inside human
cells.

\par\null

I sincerely think many surprises on this research are still to come. To
take full advantage of our research, we developed
\href{http://phosfate.com}{phosfate.com} a web interface where people
can reanalyze their own signaling data, compare it with the compiled
atlas and discover new insights on the regulatory events relevant to
their own research.

\par\null

\section*{\texorpdfstring{What are you working on now?\\
}{What are you working on now? }}\label{what-are-you-working-on-now}

Our understanding of human signaling is still very limited. During my
postdoc at \href{http://www.ebi.ac.uk/research/beltrao}{Pedro Beltrao's
lab} at \href{http://www.ebi.ac.uk}{EMBL-EBI}, I've focused on
disentangling the basis of the signaling events determining the human
decision-making using the myriad of data available nowadays. What are
the most relevant events, which players determine the outcome of the
cell or how we can influence the master regulators in order to redirect
the cellular outcomes are some of the most relevant pending scientific
questions I would like to answer.

\par\null

\section*{\texorpdfstring{Was there a key reason why you decided to write
your article on Authorea?~ What were some of the features you liked?\\
}{Was there a key reason why you decided to write your article on Authorea?~ What were some of the features you liked? }}\label{was-there-a-key-reason-why-you-decided-to-write-your-article-on-authorea-what-were-some-of-the-features-you-liked}

This work is a collaboration between our lab based in Cambridge (UK),
Silvia Santos' lab in London (UK), Judit Vill\selectlanguage{ngerman}én's lab in Seattle (WA)
and Athanasios Typas' lab in Heidelberg (Germany). With people
collaborating in 4 different locations, we required a platform that
would allow us to simultaneously access the same document in a visually
friendly interface and take advantage of the low-level Markdown/LaTeX
editing. Authorea worked perfectly, some authors could edit the document
in the website without knowing they were contributing to a LaTeX
compiled document. Additionally, the manuscript was hooked to the same
Github project where all the data analysis code was hosted. But the true
benefits of using Authorea came when formatting the manuscripts for
publication. Both the \href{http://dx.doi.org/10.1101/067900}{BiorXiv
preprint}~as well as the peer-reviewed article finally published in
\href{http://dx.doi.org/10.15252/msb.20167295}{Molecular Systems
Biology} went from live editing to publication-ready documents in the
fraction of a second. I look forward to future improvements in Authorea.
A distraction free mode for writing would be great!

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