Monthly Archives: September 2020

It’s been here all along: Analysis of the antibody DE loop

In my work, I mainly look at antigen-bound antibodies and this means a lot of analysing interfaces. Specifically, I spend a lot of my time examining the contributions of complementarity-determining regions (CDRs) to antigen binding, but what about antibodies where the framework (FW) region also contributes to binding? Such structures do exist, and these interactions are rarely trivial. As such, a recent preprint I came across where the authors examined the DE loops of antibodies was a great motivator to broaden my horizons!

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Epitope mapping with structural data for SARS-CoV-2 RBD and 10 known binders

In the past few months we have seen a lot of papers reporting antibodies that they found to bind to SARS-CoV-2 (a database can be found here: http://opig.stats.ox.ac.uk/webapps/covabdab/). Some of them were from the analysis of a patient’s immune system. Some of them come with crystal structures to show where they bind. Some don’t have structures, but they have the sequences and some competition assay data to show approximately where on the spike protein they bind. The main focus is around an area called the Receptor Binding Domain (RBD) which is where the spike protein engages the human ACE2 receptor and causes the downstream problems. In this paper, the authors ran a complete mutagenesis on the RBD of the SARS-CoV-2 spike protein. 

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PyMOL: colouring proteins by property

We all love pretty, colourful pictures of proteins. There is quite a variety of programs to produce publication-quality images of proteins, some of the most popular being VMD, PyMOL and Chimera. Each has advantages and disadvantages — for example, VMD is particularly good to deal with molecular dynamics simulations (perhaps that’s why it is called “Visual Molecular Dynamics”?), and Chimera is able to produce breathtaking graphics with very little user input. In my work, however, I tend to peruse PyMOL: a Python interface is incredibly helpful to produce quick analyses.

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Robust gene coexpression networks using signed distance correlation

Even within well-studied organisms, many genes lack useful functional annotations. One way to generate such functional information is to infer biological relationships between genes/proteins, using a network of gene coexpression data that includes functional annotations. However, the lack of trustworthy functional annotations can impede the validation of such networks. Hence, there is a need for a principled method to construct gene coexpression networks that capture biological information and are structurally stable even in the absence of functional information.

In my latest paper, we introduce the concept of signed distance correlation as a measure of dependency between two variables and apply it to generate gene coexpression networks. Distance correlation offers a more intuitive approach to network construction than commonly used methods such as Pearson correlation. We propose a framework to generate self-consistent networks using signed distance correlation purely from gene expression data, with no additional information. We analyse data from three different organisms to illustrate how networks generated with our method are more stable and capture more biological information compared to networks obtained from Pearson or Spearman correlations.

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How to SCP files from a gated server to your personal computer

Jack recently made a blog post in which he provided a script which can transfer your files between your personal computer and a given remote machine via temporarily hosting a file on file.io (blog post here); where you have some sensitive data that you do not want to risk hosting online, you can also fairly easily use SCP to keep business strictly between your local and remote machine.

What I am referring to is described here. This blog post refers to the case where you want to SCP from local host to a remote machine which is only accessible via a gate server (this isn’t necessarily true for the Stats computers as we can use the VPN to directly access our remote machine of choice by the way). I won’t effectively plagiarise the blog post I linked to as the explanation is clear enough in itself, but you just use port forwarding and the localhost address of your local machine!

Best wishes,

Eve

Curing Dogs With Cancer: The Power of the Antibody

This blog post finally combines the two great passions of my life: antibodies and dogs. Therapeutic antibody development is a huge area and is certainly not limited to humans. In the process of developing antibodies, we often use mouse or rat antibodies, obtained by injecting the animal with the antigen of choice and then collecting the resulting antibodies. The first monoclonal antibodies (mAbs) were produced in this way, by fusing spleen B cells from an immunised mouse or rabbit with immortalised myeloma cells to form antibody-expressing hybridoma cells. However, using antibodies to treat disease in animals lags behind humans.

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Re-educating myself about the light chain

I have an unconscious habit of personification, and I always see the antibody light chain as lazy for not contributing more residues to binding interfaces (obviously a generalisation – e.g. insertions in CDRL4 in anti-HIV bNAbs [1]). Perhaps this is why I have a personal preference for the more diverse [2] heavy chain with its specificity-determining [3] CDR3. Having written this down, I realised it’s actually pretty weird to consider an antibody chain as a person and I ought to re-educate myself about the role that light chains play.

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