Category Archives: Code

Crystallographic programming: Super short tour of the cctbx

Two of the leading packages in crystallography are Phenix and CCP4. For most practicing crystallographers they will interact via with these to progress a single crystallographic data-set from diffraction images, through integration, merging, phasing, model building and hopefully deposition.

However, if you want to develop crystallographic software, you will likely need to decide on a framework to build upon. Phenix is built on the comprehensive cctbx library, whereas CCP4 programs are typically standlone, although common crystallographic libraries such as clipper and cctbx are utilised.

CCTBX is written mainly in python, with core crystallographic functionality written in C++. My usual starting place for understanding functionality is through the pdb parser tutorial. This introduces the concept of a hierarchy, a iterative way to represent a macromolecule:

from iotbx.pdb import hierarchy
pdb_in = hierarchy.input(file_name="model.pdb")
for chain in pdb_in.hierarchy.only_model().chains() :
  for residue_group in chain.residue_groups() :
    for atom_group in residue_group.atom_groups() :
      for atom in atom_group.atoms() :
        if (atom.element.strip().upper() == "ZN") :
      if (atom_group.atoms_size() == 0) :
    if (residue_group.atom_groups_size() == 0) :
f = open("model_Zn_free.pdb", "w")

Although there are many ways to parse a pdb file, the introduction to iotbx.pdb, gives a view of how xray structure data can be associated to the model. The tour of the cctbx can be helpful starting place, especially for understanding how the python and c++ functionality interact through boost and the scitbx.array_family.flex. Unfortunately, documentation on cctbx tends to vary in quality and quantity throughout the modules:

Other components of the library include ways to simulate crystallographic data through simtbx,  and tools for processing xfel data.

As the library is open source, github hosted source code allows exploration of previously written routines, which can be very helpful for understanding the inner workings of the library. Note that there are also bulletin boards for users and developers of phenix and cctbx respectively. A few tutorials can also be found.

Hopefully this post will give someone other than me a reminder of where to find resources to get started developing within CCTBX.

Latexing with gvim

Here I’ll share my set-up for writing Latex with gvim instead of a separate Latex editor. If you are text-editor averse, this blog post is not for you. But if, like me, you love vim and hate useless GUIs, this might be helpful.

We’re lucky to have nice big screens in the Stats Department, but I tend to prefer writing on my MacBook (I find it’s easier to transport to e.g. a cafe, my home, etc). Until now, I’ve been happily using TexMaker for writing, but during a recent period of intense Latexing I started to find the useable screen space oppressively small. The unnecessary GUI had to go.   

No offence TexMaker but I don’t like you

One of our good friends in Statistical Genetics recommended some things to help me with the transition to just using good old (g)vim, which I will now recommend to you.

The key thing is the LaTex-Box plug-in for vim, which gives you the compilation commands, as well as the essentials such as smart indentation, highlight matching, command completion, etc. I used pathogen to install it (see the GitHub for instructions).

Of course, you can then customise your .vimrc file to add more helpful things. This can be the simple preferences, such as using a light background when using gvim:


if has(“gui_running”)

        set background=light


You can also do more complicated magic like tabbing through available commands, and the ability to minimise sections, etc. Sidenote: to make working with paragraphs easier, I recommend setting the up/down arrows to move the cursor to the next line in the GUI rather than the next actual line. I prefer overriding this behaviour only in gvim, while leaving the normal behaviour in vim (for actual coding). But each to their own.

To get started, open a .tex file, then compile and view the document with the command Latexmk.

Command suggestions are an example of a magical feature added in .vimrc

The configurations for this command are set in the file .latexmkrc. Mine looks like this:


$recorder = 1;
$pdf_mode = 1;
$bibtex_use = 2;
$pdflatex = "pdflatex --shell-escape %O %S";
$pdf_previewer = "start open -a skim %O %S";

My pdf viewer of choice on Mac is Skim, which autoupdates. I view the source and preview at the same time using split view. Please admire the beauty below:

Wow what a beautiful screen

My favourite part is that whenever you save (w), it recompiles and updates the preview. As someone who accidentally types :w everywhere that isn’t vim, it’s nice that this is now productive. It also recompiles automatically if the .bib file is updated. Note that if you have errors at compilation (I’m sure you don’t), you can view them with the command LatexErrors.

Now you too can be a (nearly) GUI-free lightweight Latexer. Enjoy!


Using Random Forests in Python with Scikit-Learn

I spend a lot of time experimenting with machine learning tools in my research; in particular I seem to spend a lot of time chasing data into random forests and watching the other side to see what comes out. In my many hours of Googling “random forest foobar” a disproportionate number of hits offer solutions implemented in R. As a young Pythonista in the present year I find this a thoroughly unacceptable state of affairs, so I decided to write a crash course in how to build random forest models in Python using the machine learning library scikit-learn (or sklearn to friends). This is far from exhaustive, and I won’t be delving into the machinery of how and why we might want to use a random forest. Rather, the hope is that this will be useful to anyone looking for a hands-on introduction to random forests (or machine learning in general) in Python.

In the future I’ll write a more in-depth post on how a few libraries turn Python into a powerful environment for data handling and machine learning. Until then, though, let’s jump into random forests!

Toy datasets

Sklearn comes with several nicely formatted real-world toy data sets which we can use to experiment with the tools at our disposal. We’ll be using the venerable iris dataset for classification and the Boston housing set for regression. Sklearn comes with a nice selection of data sets and tools for generating synthetic data, all of which are well-documented. Now, let’s write some Python!

import numpy as np
import pandas as pd
import matplotlib.pyplot as plt
import seaborn as sns

from sklearn import datasets
iris = datasets.load_iris()

Classification using random forests

First we’ll look at how to do solve a simple classification problem using a random forest. The iris dataset is probably the most widely-used example for this problem and nicely illustrates the problem of classification when some classes are not linearly separable from the others.

First we’ll load the iris dataset into a pandas dataframe. Pandas is a nifty Python library which provides a data structure comparable to the dataframes found in R with database style querying. As an added bonus, the seaborn visualization library integrates nicely with pandas allowing us to generate a nice scatter matrix of our data with minimal fuss.

df = pd.DataFrame(, columns=iris.feature_names)

# sklearn provides the iris species as integer values since this is required for classification
# here we're just adding a column with the species names to the dataframe for visualisation
df['species'] = np.array([iris.target_names[i] for i in])

sns.pairplot(df, hue='species')

Neat. Notice that iris-setosa is easily identifiable by petal length and petal width, while the other two species are much more difficult to distinguish. We could do all sorts of pre-processing and exploratory analysis at this stage, but since this is such a simple dataset let’s just fire on. We’ll do a bit of pre-processing later when we come to the Boston data set.

First, let’s split the data into training and test sets. We’ll used stratified sampling by iris class to ensure both the training and test sets contain a balanced number of representatives of each of the three classes. Sklearn requires that all features and targets be numeric, so the three classes are represented as integers (0, 1, 2). Here we’re doing a simple 50/50 split because the data are so nicely behaved. Typically however we might use a 75/25 or even 80/20 training/test split to ensure we have enough training data. In true Python style this is a one-liner.

from sklearn.model_selection import train_test_split

X_train, X_test, y_train, y_test = train_test_split(df[iris.feature_names],, test_size=0.5,, random_state=123456)

Now let’s fit a random forest classifier to our training set. For the most part we’ll use the default settings since they’re quite robust. One exception is the out-of-bag estimate: by default an out-of-bag error estimate is not computed, so we need to tell the classifier object that we want this.

If you’re used to the R implementation, or you ever find yourself having to compare results using the two, be aware that some parameter names and default settings are different between the two. Fortunately both have excellent documentation so it’s easy to ensure you’re using the right parameters if you ever need to compare models.

from sklearn.ensemble import RandomForestClassifier

rf = RandomForestClassifier(n_estimators=100, oob_score=True, random_state=123456), y_train)

Let’s see how well our model performs when classifying our unseen test data. For a random forest classifier, the out-of-bag score computed by sklearn is an estimate of the classification accuracy we might expect to observe on new data. We’ll compare this to the actual score obtained on our test data.

from sklearn.metrics import accuracy_score

predicted = rf.predict(X_test)
accuracy = accuracy_score(y_test, predicted)

print(f'Out-of-bag score estimate: {rf.oob_score_:.3}')
print(f'Mean accuracy score: {accuracy:.3}')
Out-of-bag score estimate: 0.973
Mean accuracy score: 0.933

Not bad. However, this doesn’t really tell us anything about where we’re doing well. A useful technique for visualising performance is the confusion matrix. This is simply a matrix whose diagonal values are true positive counts, while off-diagonal values are false positive and false negative counts for each class against the other.

from sklearn.metrics import confusion_matrix

cm = pd.DataFrame(confusion_matrix(y_test, predicted), columns=iris.target_names, index=iris.target_names)
sns.heatmap(cm, annot=True)

This lets us know that our model correctly separates the setosa examples, but exhibits a small amount of confusion when attempting to distinguish between versicolor and virginica.

Random forest regression

Now let’s look at using a random forest to solve a regression problem. The Boston housing data set consists of census housing price data in the region of Boston, Massachusetts, together with a series of values quantifying various properties of the local area such as crime rate, air pollution, and student-teacher ratio in schools. The question for us is whether we can use these data to accurately predict median house prices. One caveat of this data set is that the median house price is truncated at $50,000 which suggests that there may be considerable noise in this region of the data. You might want to remove all data with a median house price of $50,000 from the set and see if the regression improves at all.

As before we’ll load the data into a pandas dataframe. This time, however, we’re going to do some pre-processing of our data by independently transforming each feature to have zero mean and unit variance. The values of different features vary greatly in order of magnitude. If we were to analyse the raw data as-is, we run the risk of our analysis being skewed by certain features dominating the variance. This isn’t strictly necessary for a random forest, but will enable us to perform a more meaningful principal component analysis later. Performing this transformation in sklearn is super simple using the StandardScaler class of the preprocessing module. This time we’re going to use an 80/20 split of our data. You could bin the house prices to perform stratified sampling, but we won’t worry about that for now.

boston = datasets.load_boston()

features = pd.DataFrame(, columns=boston.feature_names)
targets =

As before, we’ve loaded our data into a pandas dataframe. Notice how I have to construct new dataframes from the transformed data. This is because sklearn is built around numpy arrays. While it’s possible to return a view of a dataframe as an array, transforming the contents of a dataframe requires a little more work. Of course, there’s a library for that, but I’m lazy so I didn’t use it this time.

from sklearn.preprocessing import StandardScaler

X_train, X_test, y_train, y_test = train_test_split(features, targets, train_size=0.8, random_state=42)

scaler = StandardScaler().fit(X_train)
X_train_scaled = pd.DataFrame(scaler.transform(X_train), index=X_train.index.values, columns=X_train.columns.values)
X_test_scaled = pd.DataFrame(scaler.transform(X_test), index=X_test.index.values, columns=X_test.columns.values)

With the data standardised, let’s do a quick principal-component analysis to see if we could reduce the dimensionality of the problem. This is quick and easy in sklearn using the PCA class of the decomposition module.

from sklearn.decomposition import PCA

pca = PCA()
cpts = pd.DataFrame(pca.transform(X_train))
x_axis = np.arange(1, pca.n_components_+1)
pca_scaled = PCA()
cpts_scaled = pd.DataFrame(pca.transform(X_train_scaled))

# matplotlib boilerplate goes here

Notice how without data standardisation the variance is completely dominated by the first principal component. With standardisation, however, we see that in fact we must consider multiple features in order to explain a significant proportion of the variance. You might want to experiment with building regression models using the principal components (or indeed just combinations of the raw features) to see how well you can do with less information. For now though we’re going to use all of the (scaled) features as the regressors for our model. As with the classification problem fitting the random forest is simple using the RandomForestRegressor class.

from sklearn.ensemble import RandomForestRegressor

rf = RandomForestRegressor(n_estimators=500, oob_score=True, random_state=0), y_train)

Now let’s see how we do on our test set. As before we’ll compare the out-of-bag estimate (this time it’s an R-squared score) to the R-squared score for our predictions. We’ll also compute Spearman rank and Pearson correlation coefficients for our predictions to get a feel for how we’re doing.

from sklearn.metrics import r2_score
from scipy.stats import spearmanr, pearsonr

predicted_train = rf.predict(X_train)
predicted_test = rf.predict(X_test)

test_score = r2_score(y_test, predicted_test)
spearman = spearmanr(y_test, predicted_test)
pearson = pearsonr(y_test, predicted_test)

print(f'Out-of-bag R-2 score estimate: {rf.oob_score_:>5.3}')
print(f'Test data R-2 score: {test_score:>5.3}')
print(f'Test data Spearman correlation: {spearman[0]:.3}')
print(f'Test data Pearson correlation: {pearson[0]:.3}')
Out-of-bag R-2 score estimate: 0.841
Test data R-2 score: 0.886
Test data Spearman correlation: 0.904
Test data Pearson correlation: 0.942

Not too bad, though there are a few outliers that would be worth looking into. Your challenge, should you choose to accept it, is to see if removing the $50,000 data improves the regression.

Wrapping up

Congratulations on making it this far. Now you know how to pre-process your data and build random forest models all from the comfort of your iPython session. I plan on writing more in the future about how to use Python for machine learning, and in particular how to make use of some of the powerful tools available in sklearn (a pipeline for data preparation, model fitting, prediction, in one line of Python? Yes please!), and how to make sklearn and pandas play nicely with minimal hassle. If you’re lucky, and if I can bring myself to process the data nicely, I might include some fun examples from less well-behaved real-world data sets.

Until then, though, happy Pythoning!

In MATLAB, it’s colormaps all the way down

My overriding emotion, working in R, has been incomprehension: incomprehension at the gallery of ugly gnomes that populate the namespace and worried puzzlement over the strange incantations required to get them to dance in a statistically harmonious way. But all that aside, I resolved, joining the group, to put aside my misgivings and give the gnomes another try.

Soon, I found myself engaged in a reassessment of my life choices. I realized that life’s too short to spend it tickling gnomes – especially when only one of them knows how to do linear regression, but he won’t tell you your p value unless you give him the right kinds of treats. I fired up MATLAB and I haven’t looked back.

However, there was issue of continued perplexity, and I’m not referring to why MATLAB insists on shouting itself at you. I need to make a lot of 2-D plots of protein distance matrices. The trouble is that I like to highlight parts of them, and that’s not straightforward in MATLAB. Let’s have a look at an example:

>> dists=dlmread('1hel.distances');
>> colormap gray;
>> imagesc(dists>8);
>> axis square;

Contact map

Now, let’s load up a set of residues and try to overlay them on top of the first image:

>> resn=dlmread('1hel.resn');
>> mask = zeros(size(dists));
>> mask(resn,resn)=1;
>> hold on
>> imagesc(1-mask, 'AlphaData',mask*.5);

So far, so easy. To review the main points:

mask is a matrix which has a one at all the pixels that we want to highlight. But we use imagesc(1-mask) because the gray colormap displays black at 0 and white at 1. If we did imagesc(mask), we would end up with grey everywhere and white only where we hoped to highlight – the opposite effect from the one that we sought.

AlphaData is a property which sets the transparency of the image. We want the image to be fully transparent where mask is 0 – so as not to fog out the underlying image – and partially transparent where mask is 1. 0.5*mask is a matrix which is 0.5 everywhere that mask is 1 and 0 everywhere else.  If we set 0.5*mask as the AlphaData property, then the colour we add will be at half transparency and the white areas will be fully transparent.

But this isn’t a very pleasant image. We want to be able to highlight the regions in some colour other than grey. Let’s try.

>> close all
>> imagesc(dists>8)
>> colormap gray
>> axis square
>> imagesc(1-mask, 'AlphaData',mask*.3,'ColorMap','jet');
Error using image
There is no ColorMap property on the Image class.

Error in imagesc (line 39)
hh = image(varargin{:},'CDataMapping','scaled');

No luck! What’s more, setting the colormap between calls to image() and imagesc() also doesn’t work. Here’s the problem: the colormap is a property of the figure, not the data. (More precisely, it is not a property of the MATLAB axes.) When you change the colormap, you change the colors of every datapoint in the image.

The fix

MATLAB’s colormap mechanism is just simple enough to be confusing. MATLAB stores colours as 1×3 vectors, where each element in the vector is the proportion of red, green, or blue, respectively. [1 1 1] is white, [0 0 0] is black, and [1 0 0] is a frightfully iridescent red. A colormap is just a list of colors – 64 will normally do – which change smoothly from from one colour to another. To have a look at the built-in MATLAB colormaps, see here.

image rounds every value in the matrix to the nearest whole number (call that number i)  and plots that pixel with the color given by colormap(i,:). Zero or below gets the first entry in the colormap and any index higher than the maximum is displayed with the last color in the colormap. So: if we construct a new colormap by concatenating two colormaps – the first running from rows 1 to 64 and the second running from 65 to 128 – if we scale our data so that the minimum is 65 and the maximum is 128, the data will never use the first set of colors. And, likewise, if we scale so that the lowest value is 1 and the highest is 64, we will use the first colormap. This seems like the sort of thing that we could manage automatically – and should, in fact. So I set myself to replace image and imagesc so that they would accept a ColorMap parameter.

How would it work?

>> colormap bone
>> imagesc(dists>8)
>> hold on
>> imagesc(mask,'ColorMap',[0.5 0 0.5],'AlphaData',0.5*(mask>0))
>> axis square


Implementation notes

  • image is implemented in the MATLAB Java source code, but imagesc is a wrapper to image, written directly in MATLAB code. Therefore, overloading image requires the new function to be placed in a special directory called @double, while imagesc can be placed anywhere (except it cannot be placed in @double). If you then want to call the original version of image(), you can use builtin(‘image’,arg1,arg2,…), whereas if you want to call the original imagesc, it is a right pain. Instead, I used type imagesc to extract the source of imagesc and I modified that source directly – obviating any need to call the original imagesc. For reference, though, the most efficient way works out to be to find the function with which('imagesc'), cd into the containing directory, create a function handle to imagesc, and then cd out. As I said, it’s a mess.
  • These edits break colorbars. I added a spacer entry in each colormap which stores the maximum and minimum ‘real’ values of the data – in case that is useful for when I get around to extending colorbar. colormap entries must be inside [0,1] so these data are stored in the first twelve decimal places of the colormap entries: a strange burlesque on floating points. It’s a hack, but for my purposes it works.
  • In addition to the standard colormaps, I often require a mask in a particular color. For this purpose it helps to have a colormap that smoothly varies from white to the color in question. It actually doesn’t matter if it varies from white or any other color – ultimately, I only use the full colour value, since I set the transparency of all other pixels to maximum – but either way, passing the colour on [0,1] scale or [0,255] scale sets a colormap which varies from white to that color.

The code is available on MATLAB File Exchange at this link and is installable by copying imagesc.mbootleg_fp.m, and the directory @double into your working directory. The idea to concatenate colormaps is widely available online – for example, here.

Using bare git repos

Git is a fantastic method of doing version control of your code. Whether it’s to share with collaborators, or just for your own reference, it almost acts as an absolute point of reference for a wide variety of applications and needs. The basic concept of git is that you have your own folder (in which you edit your code, etc.) and you commit/push those changes to a git repository. Note that Git is a version control SYSTEM and GitHub/BitBucket etc. are services that host repositories using Git as its backend!

The basic procedure of git can be summarised to:

1. Change/add/delete files in your current working directory as necessary. This is followed by a git add or git rm command.
2. “Commit” those changes; we usually put a message reflecting the change from step 1. e.g. git commit -m "I changed this file because it had a bug before."
3. You “push” those changes with git push to a git repository (e.g. hosted by BitBucket, GitHub, etc.); this is sort of like saying “save” that change.

Typically we use services like GitHub to HOST a repository. We then push our changes to that repository (or git pull from it) and all is good. However, a powerful concept to bear in mind is the ‘bare’ git repository. This is especially useful if you have code that’s private and should be strictly kept within your company/institution’s server, yet you don’t want people messing about too much with the master version of the code. The diagram below makes the bare git repository concept quite clear:

The bare repo acts as a “master” version of sorts, and every other “working”, or non-bare repo pushes/pulls changes out of it.

Let’s start with the easy stuff first. Every git repository (e.g. the one you’re working on in your machine) is a WORKING/NON-BARE git repository. This shows files in your code as you expect it, e.g. *.py or *.c files, etc. A BARE repository is a folder hosted by a server which only holds git OBJECTS. In it, you’ll never see a single .py or .c file, but a bunch of folders and text files that look nothing like your code. By the magic of git, this is easily translated as .py or .c files (basically a version of the working repo) when you git clone it. Since the bare repo doesn’t contain any of the actual code, you can safely assume that no one can really mess up with the master version without having gone through the process of git add/commit/push, making everything documented. To start a bare repo…

# Start up a bare repository in a server
user@server:$~  git init --bare name_to_repo.git

# Go back to your machine then clone it
user@machine:$~ git clone user@server:/path/to/repo/name_to_repo.git .

# This will clone a empty git repo in your machine
cd name_to_repo
# Nothing should come up.

touch README
echo "Hello world" >> README
git add README
git commit -m "Adding a README to initialise the bare repo."
git push origin master # This pushes to your origin, which is user@server:/path/to/repo/name_to_repo.git

If we check our folders, we will see the following:

user@machine:$~ ls /path/to/repo
README # only the readme exists

user@server:$~ ls /path/to/repo/name_to_repo.git/
branches/ config description HEAD hooks/ info/ objects/ refs/

Magic! README isn’t in our git repo. Again, this is because the git repo is BARE and so the file we pushed won’t exist. But when we clone it in a different machine…

user@machine2:$~ git clone user@server:/path/to/repo/name_to_repo.git .
ls name_to_repo.git/
Hello world #magic!

This was a bit of a lightning tour but hopefully you can see that the purpose of a bare repo is to allow you to host code as a “master version” without having you worry that people will see the contents directly til they do a git clone. Once they clone, and push changes, everything will be documented via git, so you’ll know exactly what’s going on!

Bitbucket and PyCharm – Tools to make a DPhil less problematic

I find Git a wonderful tool for my work, with version control providing much needed damage control to my projects. I also find Git incredibly powerful at making my working life easier, with the ability to use git push and git pull to synchronise my code between the various computers that I use for my DPhil. Via a BitBucket account, providing a remote Git repository, I am able to move my code around to wherever I am working and allow more room for either more procrastination or staring at my screen in confusion.

As simple as GIT is, it can be a fiddle entering the git commands in command line as well as remembering to do this as you rush to leave the building. This has all been made much easier with PyCharm, from JetBrains. This IDE (integrated development environment) has many tools including version control such as support for a variety of file types, PEP8 checks to ensure good quality code and its ability to work with ipython notebooks.

I’ve put the following mini-tutorial together for those who want to make or bring in an existing repository to PyCharm and get version control working:

Continue reading

A very basic introduction to Random Forests using R

Random Forests is a powerful tool used extensively across a multitude of fields. As a matter of fact, it is hard to come upon a data scientist that never had to resort to this technique at some point. Motivated by the fact that I have been using Random Forests quite a lot recently, I decided to give a quick intro to Random Forests using R.

So what are Random Forests?  Well, I am probably not the most suited person to answer this question (a google search will reveal much more interesting answers) , still I shall give it a go. Random Forests is a learning method for classification (and others applications — see below). It is based on generating a large number of decision trees, each constructed using a different subset of your training set. These subsets are usually selected by sampling at random and with replacement from the original data set. The decision trees are then used to identify a classification consensus by selecting the most common output (mode). While random forests can be used for other applications (i.e. regression), for the sake of keeping this post short, I shall focus solely on classification.

Why R? Well, the quick and easy question for this is that I do all my plotting in R (mostly because I think ggplot2 looks very pretty). I decided to explore Random Forests in R and to assess what are its advantages and shortcomings. I am planning to compare Random Forests in R against the python implementation in scikit-learn. Do expect a post about this in the near future!

The data: to keep things simple, I decided to use the Edgar Anderson’s Iris Data set. You can have a look at it by inspecting the contents of iris in R. This data set contains observations for four features (sepal length and width, and petal length and width – all in cm) of 150 flowers, equally split between three different iris species. This data set is fairly canon in classification and data analysis. Let us take a look at it, shall we:

As you can observe, there seems to be some separation in regards to the different features and our three species of irises [note: this set is not very representative of a real world data set and results should be taken with a grain of salt].

Training and Validation sets: great care needs to be taken to ensure clear separation between training and validation sets. I tend to save the cases for which I am actually interested in performing predictions as a second validation set (Validation 2). Then I split the remaining data evenly into Training and Validation 1.

Let us split our data set then, shall we?

# Set random seed to make results reproducible:
# Calculate the size of each of the data sets:
data_set_size <- floor(nrow(iris)/2)
# Generate a random sample of "data_set_size" indexes
indexes <- sample(1:nrow(iris), size = data_set_size)

# Assign the data to the correct sets
training <- iris[indexes,]
validation1 <- iris[-indexes,]

Before we can move on, here are some things to consider:

1- The size of your data set usually imposes a hard limit on how many features you can consider. This occurs due to the curse of dimensionality, i.e. your data becomes sparser and sparser as you increase the number of features considered, which usually leads to overfitting. While there is no rule of thumb relating to how many features vs.  the number of observations you should use, I try to keep e^Nf < No (Nf = number of features, No = number of observations) to minimise overfitting [this is not always possible and it does not ensure that we won’t overfit]. In this case, our training set has 75 observations, which suggests that using four features (e^4 ~ 54.6) is not entirely absurd. Obviously, this depends on your data, so we will cover some further overfitting checks later on.

2- An important thing to consider when assembling training sets is the proportion of negatives vs. positives in your data. Think of an extreme scenario where you have many, many more observations for one class vs. the others. How will this affect classification? This would make it more likely for the classifier to predict the dominant class when given new values. I mentioned before that the iris set is quite nice to play with. It comes with exactly 50 observations for each species of irises. What happens if you have a data set with a much higher number of observations for a particular class? You can bypass any imbalance regarding the representation of each class by carefully constructing your training set in order not to favour any particular class. In this case, our randomly selected set has 21 observations for species setosa and 27 observations for each of species versicolor and virginica, so we are good to go.

3- Another common occurrence that is not represented by the iris data set is missing values (NAs) for observations. There are many ways of dealing with missing values, including assigning the median or the mode for that particular feature to the missing observation or even disregarding some observations entirely, depending on how many observations you have. There are even ways to use random forests to estimate a good value to assign to the missing observations, but for the sake of brevity, this will not be covered here.

Right, data sets prepared and no missing values, it is time to fire our random forests algorithm. I am using the  randomForest package. You can click the link for additional documentation. Here is the example usage code:

#import the package
# Perform training:
rf_classifier = randomForest(Species ~ ., data=training, ntree=100, mtry=2, importance=TRUE)

Note some important parameters:

-The first parameter specifies our formula: Species ~ . (we want to predict Species using each of the remaining columns of data).
ntree defines the number of trees to be generated. It is typical to test a range of values for this parameter (i.e. 100,200,300,400,500) and choose the one that minimises the OOB estimate of error rate.
mtry is the number of features used in the construction of each tree. These features are selected at random, which is where the “random” in “random forests” comes from. The default value for this parameter, when performing classification, is sqrt(number of features).
importance enables the algorithm to calculate variable importance.

We can quickly look at the results of our classifier for our training set by printing the contents of rf_classifier:

> rf_classifier

 randomForest(formula = Species ~ ., data = training,ntree=100,mtry=2, importance = TRUE) 
               Type of random forest: classification
                     Number of trees: 100
No. of variables tried at each split: 2

        OOB estimate of  error rate: 5.33%
Confusion matrix:
           setosa versicolor virginica class.error
setosa         21          0         0  0.00000000
versicolor      0         25         2  0.07407407
virginica       0          2        25  0.07407407

As you can see, it lists the call used to build the classifier, the number of trees (100), the variables at each split (2), and it outputs a very useful confusion matrix and OOB estimate of error rate. This estimate is calculated by counting however many points in the training set were misclassified (2 versicolor and 2 virginica observations = 4) and dividing this number by the total number of observations (4/75 ~= 5.33%).

The OOB estimate of error rate is a useful measure to discriminate between different random forest classifiers. We could, for instance, vary the number of trees or the number of variables to be considered, and select the combination that produces the smallest value for this error rate. For more complicated data sets, i.e. when a higher number of features is present, a good idea is to use cross-validation to perform feature selection using the OOB error rate (see rfcv from randomForest for more details).

Remember the importance parameter? Let us take a look at the importance that our classifier has assigned to each variable:


Each features’s importance is assessed based on two criteria:

-MeanDecreaseAccuracy: gives a rough estimate of the loss in prediction performance when that particular variable is omitted from the training set. Caveat: if two variables are somewhat redundant, then omitting one of them may not lead to massive gains in prediction performance, but would make the second variable more important.

-MeanDecreaseGini: GINI is a measure of node impurity. Think of it like this, if you use this feature to split the data, how pure will the nodes be? Highest purity means that each node contains only elements of a single class. Assessing the decrease in GINI when that feature is omitted leads to an understanding of how important that feature is to split the data correctly.

Do note that these measures are used to rank variables in terms of importance and, thus, their absolute values could be disregarded.

Ok, great. Looks like we have a classifier that was properly trained and is producing somewhat good predictions for our training set. Shall we evaluate what happens when we try to use this classifier to predict classes for our  validation1 set?

# Validation set assessment #1: looking at confusion matrix
prediction_for_table <- predict(rf_classifier,validation1[,-5])

observed     setosa versicolor virginica
  setosa         29          0         0
  versicolor      0         20         3
  virginica       0          1        22

The confusion matrix is a good way of looking at how good our classifier is performing when presented with new data.

Another way of assessing the performance of our classifier is to generate a ROC curve and compute the area under the curve:


# Validation set assessment #2: ROC curves and AUC

# Needs to import ROCR package for ROC curve plotting:

# Calculate the probability of new observations belonging to each class
# prediction_for_roc_curve will be a matrix with dimensions data_set_size x number_of_classes
prediction_for_roc_curve <- predict(rf_classifier,validation1[,-5],type="prob")

# Use pretty colours:
pretty_colours <- c("#F8766D","#00BA38","#619CFF")
# Specify the different classes 
classes <- levels(validation1$Species)
# For each class
for (i in 1:3)
 # Define which observations belong to class[i]
 true_values <- ifelse(validation1[,5]==classes[i],1,0)
 # Assess the performance of classifier for class[i]
 pred <- prediction(prediction_for_roc_curve[,i],true_values)
 perf <- performance(pred, "tpr", "fpr")
 if (i==1)
     plot(perf,main="ROC Curve",col=pretty_colours[i]) 
     plot(perf,main="ROC Curve",col=pretty_colours[i],add=TRUE) 
 # Calculate the AUC and print it to screen
 auc.perf <- performance(pred, measure = "auc")

Here is the final product (ROC curve):

And here are the values for our AUCs:

AUC = 1

AUC = 0.98

AUC = 0.98

Voila! I hope this was somewhat useful!

Parallel Computing: GNU Parallel

Recently I started using the OPIG servers to run the algorithm I have developed (CRANkS) on datasets from DUDE (Database of Useful Decoys Enhanced).

This required learning how to run jobs in parallel. Previously I had been using computer clusters with their own queuing system (Torque/PBS) which allowed me to submit each molecule to be scored by the algorithm as a separate job. The queuing system would then automatically allocate nodes to jobs and execute jobs accordingly. On a side note I learnt how to submit these jobs an array, which was preferable to submitting ~ 150,000 separate jobs:

qsub -t 1:X

where the contents of would be:


which would submit jobs to, where X is the total number of jobs.

However the OPIG servers do not have a global queuing system to use. I needed a way of being able to run the code I already had in parallel with minimal changes to the workflow or code itself. There are many ways to run jobs in parallel, but to minimise work for myself, I decided to use GNU parallel [1].

This is an easy-to-use shell tool, which I found quick and easy to install onto my home server, allowing me to access it on each of the OPIG servers.

To use it I simply run the command:

cat | parallel -j Y

where Y is the number of cores to run the jobs on, and contains:


This executes each job making use of Y number of cores when available to run the jobs in parallel.

Quick, easy, simple and minimal modifications needed! Thanks to Jin for introducing me to GNU Parallel!

[1] O. Tange (2011): GNU Parallel – The Command-Line Power Tool, The USENIX Magazine, February 2011:42-47.

Interesting Jupyter and IPython Notebooks

Here’s a treasure trove of interesting Jupyter and iPython notebooks, with lots of diverse examples relevant to OPIG, including an RDKit notebook, but also:

Entire books or other large collections of notebooks on a topic (covering Introductory Tutorials; Programming and Computer Science; Statistics, Machine Learning and Data Science; Mathematics, Physics, Chemistry, Biology; Linguistics and Text Mining; Signal Processing; Scientific computing and data analysis with the SciPy Stack; General topics in scientific computing; Machine Learning, Statistics and Probability; Physics, Chemistry and Biology; Data visualization and plotting; Mathematics; Signal, Sound and Image Processing; Natural Language Processing; Pandas for data analysis); General Python Programming; Notebooks in languages other than Python (Julia; Haskell; Ruby; Perl; F#; C#); Miscellaneous topics about doing various things with the Notebook itself; Reproducible academic publications; and lots more!  


Using RDKit to load ligand SDFs into Pandas DataFrames

If you have downloaded lots of ligand SDF files from the PDB, then a good way of viewing/comparing all their properties would be to load it into a Pandas DataFrame.

RDKit has a very handy function just for this – it’s found under the PandasTool module.

I show an example below within Jupypter-notebook, in which I load in the SDF file, view the table of molecules and perform other RDKit functions to the molecules.

First import the PandasTools module:

from rdkit.Chem import PandasTools

Read in the SDF file:

SDFFile = "./Ligands_noHydrogens_noMissing_59_Instances.sdf"
BRDLigs = PandasTools.LoadSDF(SDFFile)

You can see the whole table by calling the dataframe:


The ligand properties in the SDF file are stored as columns. You can view what these properties are, and in my case I have loaded 59 ligands each having up to 26 properties:

It is also very easy to perform other RDKit functions on the dataframe. For instance, I noticed there is no heavy atom column, so I added my own called ‘NumHeavyAtoms’:

BRDLigs['NumHeavyAtoms']=BRDLigs.apply(lambda x: x['ROMol'].GetNumHeavyAtoms(), axis=1)

Here is the column added to the table, alongside columns containing the molecules’ SMILES and RDKit molecule: