Research AreasPublications

DNA labeling is a tool in molecular biology and biotechnology to visualize, detect, and study DNA at the molecular level. In this process, a DNA molecule is labeled by a set of specific patterns, referred to as labels, and is then imaged. The resulting image is modeled as an (ℓ+1)-ary sequence, where ℓ is the number of labels, in which any non-zero symbol indicates the appearance of the corresponding label in the DNA molecule. The labeling capacity refers to the maximum information rate that can be achieved by the labeling process for any given set of labels. The main goal of this paper is to study the minimum number of labels of the same length required to achieve the maximum labeling capacity of 2 for DNA sequences or log2q for an arbitrary alphabet of size q. The solution to this problem requires the study of path unique subgraphs of the de Bruijn graph with the largest number of edges and we provide upper and lower bounds on this value.

Motivation

Optical genome mapping (OGM) is a technique that extracts partial genomic information from optically imaged and linearized DNA fragments containing fluorescently labeled short sequence patterns. This information can be used for various genomic analyses and applications, such as the detection of structural variations and copy-number variations, epigenomic profiling, and microbial species identification. Currently, the choice of labeled patterns is based on the available biochemical methods and is not necessarily optimized for the application.

Results

In this work, we develop a model of OGM based on information theory, which enables the design of optimal labeling patterns for specific applications and target organism genomes. We validated the model through experimental OGM on human DNA and simulations on bacterial DNA. Our model predicts up to 10-fold improved accuracy by optimal choice of labeling patterns, which may guide future development of OGM biochemical labeling methods and significantly improve its accuracy and yield for applications such as epigenomic profiling and cultivation-free pathogen identification in clinical samples.

DNA labeling is a powerful tool in molecular biology and biotechnology that allows for the visualization, detection, and study of DNA at the molecular level. Under this paradigm, a DNA molecule is being labeled by specific k patterns and is then imaged. Then, the resulted image is modeled as a (k +1)-ary sequence in which any non-zero symbol indicates on the appearance of the corresponding label in the DNA molecule. The primary goal of this work is to study the labeling capacity, which is defined as the maximal information rate that can be obtained using this labeling process. The labeling capacity is computed for any single label and several results are provided for multiple labels as well. Moreover, we provide the optimal minimal number of labels of length one or two that are needed in order to gain labeling capacity of 2.