Recovering Sparse Signals Using Sparse Measurement Matrices in Compressed DNA Microarrays

Microarrays (DNA, protein, etc.) are massively parallel affinity-based biosensors capable of detecting and quantifying a large number of different genomic particles simultaneously. Among them, DNA microarrays comprising tens of thousands of probe spots are currently being employed to test multitude of targets in a single experiment. In conventional microarrays, each spot contains a large number of copies of a single probe designed to capture a single target, and, hence, collects only a single data point. This is a wasteful use of the sensing resources in comparative DNA microarray experiments, where a test sample is measured relative to a reference sample. Typically, only a fraction of the total number of genes represented by the two samples is differentially expressed, and, thus, a vast number of probe spots may not provide any useful information. To this end, we propose an alternative design, the so-called compressed microarrays, wherein each spot contains copies of several different probes and the total number of spots is potentially much smaller than the number of targets being tested. Fewer spots directly translates to significantly lower costs due to cheaper array manufacturing, simpler image acquisition and processing, and smaller amount of genomic material needed for experiments. To recover signals from compressed microarray measurements, we leverage ideas from compressive sampling. For sparse measurement matrices, we propose an algorithm that has significantly lower computational complexity than the widely used linear-programming-based methods, and can also recover signals with less sparsity

Sparse measurements, compressed sampling, and DNA microarrays

DNA microarrays comprising tens of thousands of probe spots are currently being employed to test multitude of targets in a single experiment. Typically, each microarray spot contains a large number of copies of a single probe designed to capture a single target, and hence collects only a single data point. This is a wasteful use of the sensing resources in comparative DNA microarray experiments, where a test sample is measured relative to a reference sample. Since only a small fraction of the total number of genes represented by the two samples is differentially expressed, a vast number of probe spots will not provide any useful information. To this end we consider an alternative design, the so-called compressed microarrays, wherein each spot is a composite of several different probes and the total number of spots is potentially much smaller than the number of targets being tested. Fewer spots directly translates to significantly lower costs due to cheaper array manufacturing, simpler image acquisition and processing, and smaller amount of genomic material needed for experiments. To recover signals from compressed microarray measurements, we leverage ideas from compressive sampling. Moreover, we propose an algorithm which has far less computational complexity than the widely-used linear-programming-based methods, and can also recover signals with less sparsity

On Recovery of Sparse Signals in Compressed DNA Microarrays

Currently, DNA micro arrays comprising tens of thousands of probe spots are employed to test entire genomes in a single experiment. Typically, each microarray spot contains a large number of copies of a single probe, and hence collects only a single data point. This is a wasteful use of the sensing resources in comparative DNA microarray experiments, where a test sample is measured relative to a reference sample. Since only a small fraction of the total number of genes represented by the two samples is differentially expressed, a large fraction of a microarray does not provide any useful information. To this end, in this paper we consider an alternative microarray design wherein each spot is a composite of several different probes, and the total number of spots is potentially much smaller than the number of genes being tested. Fewer spots directly translates to significantly lower costs due to cheaper array manufacturing, simpler image acquisition and processing, and smaller amount of genomic material needed for experiments. To recover signals from compressed microarray measurements, we leverage ideas from compressive sampling. Experimental verification of the proposed methodology is presented

Compressive Sensing DNA Microarrays

Compressive sensing microarrays (CSMs) are DNA-based sensors that operate using group testing and compressive sensing (CS) principles. In contrast to conventional DNA microarrays, in which each genetic sensor is designed to respond to a single target, in a CSM, each sensor responds to a set of targets. We study the problem of designing CSMs that simultaneously account for both the constraints from CS theory and the biochemistry of probe-target DNA hybridization. An appropriate cross-hybridization model is proposed for CSMs, and several methods are developed for probe design and CS signal recovery based on the new model. Lab experiments suggest that in order to achieve accurate hybridization profiling, consensus probe sequences are required to have sequence homology of at least 80% with all targets to be detected. Furthermore, out-of-equilibrium datasets are usually as accurate as those obtained from equilibrium conditions. Consequently, one can use CSMs in applications in which only short hybridization times are allowed

Compressive Sensing DNA Microarrays

sensors that operate using group testing and compressive sensing (CS) principles. In contrast to conventional DNA microarrays, in which each genetic sensor is designed to respond to a single target, in a CSM each sensor responds to a set of targets. We study the problem of designing CSMs that simultaneously account for both the constraints from compressive sensing theory and the biochemistry of probe-target DNA hybridization. An appropriate cross-hybridization model is proposed for CSMs, and several methods are developed for probe design and CS signal recovery based on the new model. Our lab experiments suggest that, in order to achieve accurate hybridization profiling, consensus probe sequences are required to have sequence homology of at least 80 % with all targets to be detected. Furthermore, outof-equilibrium datasets are usually as accurate as those obtained from equilibrium conditions. Consequently, one can use CSMs in applications for which only short hybridization times are allowed. Index Terms—Compressive sensing, DNA microarray, group testing, hybridization affinity, probe design I

Applications of Sparse Representations

In this dissertation I explore the properties and uses of sparse representations. Sparse representations use high dimensional binary vectors for representing information. They have many properties which make this representation useful for applications involving pattern recognition in highly noisy and complex environments. Sparse representations have a very high capacity. A typical sparse representation vector has a capacity of 10^84 distinct vectors, which is more than the number of atoms in the universe. Sparse representations are highly noise robust. They can tolerate even up to 50% noise. A very powerful and useful property of sparse representations is that they allow us to easily measure similarity between two things by directly comparing their representations. These properties allow them to have applications in a variety of fields, like Artificial Intelligence and Molecular Biology, that need to encode information that is complex and noisy in nature. In this dissertation, I show how sparse representations can be used for representing complex environments for an agent based on Learning Intelligent Decision Agent (LIDA) model. Sparse representations allowed us to achieve a two-fold goal of producing information rich representations of things in the environment while proposing a method of generating grounded representations for the LIDA model. Sparse representations also allowed us to ground the representations used by LIDA in the sensory apparatus of the agent while still allowing a perfect fidelity communication between the sensory memory of LIDA and the rest of the model. I also show how sparse representations are useful in Molecular Biology for discovering data-driven patterns in heterogeneous and noisy gene expression data. We used a sparse auto-encoder to learn sparse representations of transcriptomics experiments taken from a huge publicly available dataset. These representations were then used to identify biological patterns in the form of gene sets. The representation provided a unique signature for a set of samples originating from the same experimental condition. Applications of our method include the identification of previously undiscovered gene sets as well as supervised classification of samples from different biological classes. Overall, our results show that sparse representations are useful in a variety of fields that involve finding patterns in a complex and noisy environment

Recent Advances in Hybrid Biomimetic Polymer-Based Films: from Assembly to Applications

Biological membranes, in addition to being a cell boundary, can host a variety of proteins that are involved in different biological functions, including selective nutrient transport, signal transduction, inter- and intra-cellular communication, and cell-cell recognition. Due to their extreme complexity, there has been an increasing interest in developing model membrane systems of controlled properties based on combinations of polymers and different biomacromolecules, i.e., polymer-based hybrid films. In this review, we have highlighted recent advances in the development and applications of hybrid biomimetic planar systems based on different polymeric species. We have focused in particular on hybrid films based on (i) polyelectrolytes, (ii) polymer brushes, as well as (iii) tethers and cushions formed from synthetic polymers, and (iv) block copolymers and their combinations with biomacromolecules, such as lipids, proteins, enzymes, biopolymers, and chosen nanoparticles. In this respect, multiple approaches to the synthesis, characterization, and processing of such hybrid films have been presented. The review has further exemplified their bioengineering, biomedical, and environmental applications, in dependence on the composition and properties of the respective hybrids. We believed that this comprehensive review would be of interest to both the specialists in the field of biomimicry as well as persons entering the field

Advances in Microfluidics and Lab-on-a-Chip Technologies

Advances in molecular biology are enabling rapid and efficient analyses for effective intervention in domains such as biology research, infectious disease management, food safety, and biodefense. The emergence of microfluidics and nanotechnologies has enabled both new capabilities and instrument sizes practical for point-of-care. It has also introduced new functionality, enhanced sensitivity, and reduced the time and cost involved in conventional molecular diagnostic techniques. This chapter reviews the application of microfluidics for molecular diagnostics methods such as nucleic acid amplification, next-generation sequencing, high resolution melting analysis, cytogenetics, protein detection and analysis, and cell sorting. We also review microfluidic sample preparation platforms applied to molecular diagnostics and targeted to sample-in, answer-out capabilities

Advanced Image Acquisition, Processing Techniques and Applications

"Advanced Image Acquisition, Processing Techniques and Applications" is the first book of a series that provides image processing principles and practical software implementation on a broad range of applications. The book integrates material from leading researchers on Applied Digital Image Acquisition and Processing. An important feature of the book is its emphasis on software tools and scientific computing in order to enhance results and arrive at problem solution