The Library of Integrative Network-based Cellular Signatures (LINCS) is an NIH Common Fund program. The idea is to perturb different types of human cells with many different types of perturbations such as: drugs and other small molecules; genetic manipulations such as knockdown or overexpression of single genes; manipulation of the extracellular microenvironment conditions, for example, growing cells on different surfaces, and more. These perturbations are applied to various types of human cells including induced pluripotent stem cells from patients, differentiated into various lineages such as neurons or cardiomyocytes. Then, to better understand the molecular networks that are affected by these perturbations, changes in level of many different variables are measured including: mRNAs, proteins, and metabolites, as well as cellular phenotypic changes such as changes in cell morphology. The BD2K-LINCS Data Coordination and Integration Center (DCIC) is commissioned to organize, analyze, visualize and integrate this data with other publicly available relevant resources. In this course we briefly introduce the DCIC and the various Centers that collect data for LINCS. We then cover metadata and how metadata is linked to ontologies. We then present data processing and normalization methods to clean and harmonize LINCS data. This follow discussions about how data is served as RESTful APIs. Most importantly, the course covers computational methods including: data clustering, gene-set enrichment analysis, interactive data visualization, and supervised learning. Finally, we introduce crowdsourcing/citizen-science projects where students can work together in teams to extract expression signatures from public databases and then query such collections of signatures against LINCS data for predicting small molecules as potential therapeutics.
Benchmarking | Part 2
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來自 Icahn School of Medicine at Mount Sinai 的課程
Big Data Science with the BD2K-LINCS Data Coordination and Integration Center
10 個評分
Icahn School of Medicine at Mount Sinai
10 個評分
從本節課中
Benchmarking
This module discusses how Bioinformatics pipelines can be compared and evaluated.
與講師見面
Avi Ma’ayan, PhDDirector, Mount Sinai Center for Bioinformatics
Professor, Department of Pharmacological Sciences
[SOUND] As benchmarking has become
more developed in bioinformatics,
a certain number of generally
desirable properties for
benchmark tests have been proposed,
so let's take a moment to
consider some of those now.
First, relevance, the relevance of the benchmark test is very important.
It's important that the benchmark test should address real world problems.
The issue of synthetic data versus real data is relevant here.
Benchmark tests that are based on real biological data
are preferable as they are above synthetic data.
As they are closer to the real world problems at hand.
Second, solvability, it's important that the benchmarking
test should be not too easy and not too difficult in order that
different algorithms can be discriminated against.
If the benchmark test is too easy, all tools will perform very well and
it would not be possible to choose among them.
And this will defeat the object of the benchmark test and the same goes for
if the benchmark test is too difficult.
Thirdly, accessibility.
The benchmark test needs to be very widely available.
It would defeat the object of the benchmark if it was only applied to
a small set of tools or algorithms.
The whole point of the benchmark test is that all tools and
algorithms can be compared in a standardized uniform matter.
Fourth, scalability, as, particularly in bioinformatics, which
is a burgeoning field, as progress is made in the development of algorithms and
tools, it's important that the benchmark doesn't become instantly obsolete.
So the benchmark task should be extensible so that,
the current methods and future methods, can be compared with each other.
Fifth, independence, it's a matter of circularity
that the benchmark tests should not be informed
by the very methods to be tested by that benchmark.
And lastly, evolution, it's important that
a benchmark should be continually updated.
Otherwise, what might happen is that tools and
algorithms were developed to do very well in the benchmark test,
under the very specific gold standard of the benchmark test,
but this will be an over-fitting scenario in that the tools and
algorithms will not generalize so well.
As I mentioned before, in bioinformatics, there's a very wide range of biological
questions for which algorithms and tools have been designed to address.
And each of these biological questions needs its own benchmark.
Here what I'm going to do is I'm going to sort of narrow down the scope of that.
So instead of dealing with all the questions of 3D protein structure.
The multiple sequence alignments in image analysis, I'm just going to consider
a couple of biological questions, and demonstrate some of the efforts
that have been made to make benchmarking tests in these limited scenarios.
The first one I'm going to consider, the first case study, is
benchmark test for the prediction of protein biological function.
Now the object of these methods is essentially
a supervised machine learning classifier that takes in biological data.
And tries to predict the biological function of proteins.
In order to benchmark such methods, the authors of Huttenhower et al.,
devised a benchmark data set for protein function prediction.
What the authors did is they took micro-array data and
other genomic data and provided those as inputs to
a suite of protein function prediction algorithms.
The results of the predictions were then tested experimentally
and the results were then used to generate a gold standard.
This gold standard was then used and re-input
into the protein function prediction algorithms in order
to further improve the predictions which were experimentally validated and
so on, so the process was iterated and there was an iterative improvement
in the resulting gold standard of protein function.
The result of this is a set of proteins with associated biological functions
that are very high confidence, and these can be treated as a ground truth.
And the capability of protein function
supervise machine learning classifies to recover this ground truth
in their analysis can then be used as a measure of
the performance of the machine learning classifier.
Interestingly, the authors of this paper noticed that their initial predictions of
protein function was actually better than it first seemed.
And this was because, there was an incomplete knowledge of the ground truth.
So they were, initially recovering protein functions,
which they didn't know were correct.
The second example we'll look at is in the context
of the analysis of a matrix microarray data.
Microarrays work by hybridizing RNA to a chip which contains an array of probes.
And there are multiple probes that correspond to each individual gene.
The probe level, hybridization data,
must then be summarized to produce an estimate for
the expression level of the given gene.
And there are different competing methods for performing this summarization process.
In addition to this there is also the normalization process
which I describe about in another talk.
In normalization, the aim is to remove as much
non-biological sources of variation as possible.
And there are different methods for achieving this.
So the Affycomp benchmark is designed to test the performance of summarization and
normalization of half a matrix microarray data.
And it does this with a series of graphics.
You can find out more about the Affycomp
benchmark suite from these websites.
[MUSIC]
