Entropy is a Simple Measure of the Antibody Profile and is an Indicator of Health Status: A Proof of Concept

Abstract

We have previously shown that the diversity of antibodies in an individual can be displayed on chips on which 130,000 peptides chosen from random sequence space have been synthesized. This immunosignature technology is unbiased in displaying antibody diversity relative to natural sequence space, and has been shown to have diagnostic and prognostic potential for a wide variety of diseases and vaccines. Here we show that a global measure such as Shannon’s entropy can be calculated for each immunosignature. The immune entropy was measured across a diverse set of 800 people and in 5 individuals over 3 months. The immune entropy is affected by some population characteristics and varies widely across individuals. We find that people with infections or breast cancer, generally have higher entropy values than non-diseased individuals. We propose that the immune entropy as measured from immunosignatures may be a simple method to monitor health in individuals and populations.

Using Frameshift Peptide Arrays for Cancer Neo-Antigens Screening

“…3B ), which further validated our assumptions since lymphoma evolves from a single population of lymphocytes. Another report also demonstrated that lymphoma had a distinct humoral profile compared to other cancer types 19 .…”

Antibody characterization using immunosignatures

“…We asked whether information theory could provide some insight into the behavior of the monoclonals. Here we used Shannon's entropy [17] to explore how many independent binding events could be examined together to form a picture of antibody behavior. When examined along with the histograms of the data, a picture emerges of how a given antibody responds to random sequences.…”

“…For example, the entropy score for an immunosignature increases (more randomness) as additional monoclonals were added to the solution that bound to the microarray. Thus, for a single monoclonal, an entropy score would be high if that monoclonal were more promiscuous, but also a strong binder [17]. The antibody p53 Ab8 had the highest relative entropy score across all libraries and has shown strong and very specific binding to very few peptides, generally…”

“…We settled upon Shannon's Entropy as it provided a wide range of values that should indicate diversity of information content. We applied Shannon's Entropy [17] to the patterns of data for each monoclonal for each random peptide library. Entropy is highly dependent on the composition of the library, thus there are larger differences in the score between libraries than between antibodies using the same library.…”

“…The table below lists seven different numerical descriptors of the full dataset from each peptide microarray library (330K short peptide, 330K long peptide, 125K short peptide, 124K short peptide), and for each antibody. In order, the descriptors are: Shannon's Entropy [17], 95 th percentile coefficient of variance (calculated from the standard deviation / mean of the 95 th upper percentile of all observed fluorescence intensities for each antibody per peptide library), the mean of all intensities, the stdev of all intensities, the measured kurtosis of all raw intensities, the skewness of the raw intensity data distribution, and the dynamic range of the raw intensities.…”