Genomics and proteomics: a signal processor's tour

The theory and methods of signal processing are becoming increasingly important in molecular biology. Digital filtering techniques, transform domain methods, and Markov models have played important roles in gene identification, biological sequence analysis, and alignment. This paper contains a brief review of molecular biology, followed by a review of the applications of signal processing theory. This includes the problem of gene finding using digital filtering, and the use of transform domain methods in the study of protein binding spots. The relatively new topic of noncoding genes, and the associated problem of identifying ncRNA buried in DNA sequences are also described. This includes a discussion of hidden Markov models and context free grammars. Several new directions in genomic signal processing are briefly outlined in the end

ART Neural Networks for Remote Sensing Image Analysis

ART and ARTMAP neural networks for adaptive recognition and prediction have been applied to a variety of problems, including automatic mapping from remote sensing satellite measurements, parts design retrieval at the Boeing Company, medical database prediction, and robot vision. This paper features a self-contained introduction to ART and ARTMAP dynamics. An application of these networks to image processing is illustrated by means of a remote sensing example. The basic ART and ARTMAP networks feature winner-take-all (WTA) competitive coding, which groups inputs into discrete recognition categories. WTA coding in these networks enables fast learning, which allows the network to encode important rare cases but which may lead to inefficient category proliferation with noisy training inputs. This problem is partially solved by ART-EMAP, which use WTA coding for learning but distributed category representations for test-set prediction. Recently developed ART models (dART and dARTMAP) retain stable coding, recognition, and prediction, but allow arbitrarily distributed category representation during learning as well as performance

Bioactive peptide design using the Resonant Recognition Model

With a large number of DNA and protein sequences already known, the crucial question is to find out how the biological function of these macromolecules is "written" in the sequence of nucleotides or amino acids. Biological processes in any living organism are based on selective interactions between particular bio-molecules, mostly proteins. The rules governing the coding of a protein's biological function, i.e. its ability to selectively interact with other molecules, are still not elucidated. In addition, with the rapid accumulation of databases of protein primary structures, there is an urgent need for theoretical approaches that are capable of analysing protein structure-function relationships. The Resonant Recognition Model (RRM) [1,2] is one attempt to identify the selectivity of protein interactions within the amino acid sequence. The RRM [1,2] is a physico-mathematical approach that interprets protein sequence linear information using digital signal processing methods. In the RRM the protein primary structure is represented as a numerical series by assigning to each amino acid in the sequence a physical parameter value relevant to the protein's biological activity. The RRM concept is based on the finding that there is a significant correlation between spectra of the numerical presentation of amino acids and their biological activity. Once the characteristic frequency for a particular protein function/interaction is identified, it is possible then to utilize the RRM approach to predict the amino acids in the protein sequence, which predominantly contribute to this frequency and thus, to the observed function, as well as to design de novo peptides having the desired periodicities. As was shown in our previous studies of fibroblast growth factor (FGF) peptidic antagonists [2,3] and human immunodeficiency virus (HIV) envelope agonists [2,4], such de novo designed peptides express desired biological function. This study utilises the RRM computational approach to the analysis of oncogene and proto-oncogene proteins. The results obtained have shown that the RRM is capable of identifying the differences between the oncogenic and proto-oncogenic proteins with the possibility of identifying the "cancer-causing" features within their protein primary structure. In addition, the rational design of bioactive peptide analogues displaying oncogenic or proto-oncogenic-like activity is presented here

ART and ARTMAP Neural Networks for Applications: Self-Organizing Learning, Recognition, and Prediction

ART and ARTMAP neural networks for adaptive recognition and prediction have been applied to a variety of problems. Applications include parts design retrieval at the Boeing Company, automatic mapping from remote sensing satellite measurements, medical database prediction, and robot vision. This chapter features a self-contained introduction to ART and ARTMAP dynamics and a complete algorithm for applications. Computational properties of these networks are illustrated by means of remote sensing and medical database examples. The basic ART and ARTMAP networks feature winner-take-all (WTA) competitive coding, which groups inputs into discrete recognition categories. WTA coding in these networks enables fast learning, that allows the network to encode important rare cases but that may lead to inefficient category proliferation with noisy training inputs. This problem is partially solved by ART-EMAP, which use WTA coding for learning but distributed category representations for test-set prediction. In medical database prediction problems, which often feature inconsistent training input predictions, the ARTMAP-IC network further improves ARTMAP performance with distributed prediction, category instance counting, and a new search algorithm. A recently developed family of ART models (dART and dARTMAP) retains stable coding, recognition, and prediction, but allows arbitrarily distributed category representation during learning as well as performance.National Science Foundation (IRI 94-01659, SBR 93-00633); Office of Naval Research (N00014-95-1-0409, N00014-95-0657

Investigation of the mechanisms of electromagnetic field interaction with proteins

In our earlier work we have proposed that protein activation is electromagnetic in its nature. This prediction is based on the resonant recognition model (RRM) where proteins are analyzed using digital signal processing (DSP) methods applied to the distribution of free electron energies along the protein sequence. This postulate is investigated here by applying the electromagnetic radiation to example of L-lactate dehydrogenase protein and its biological activity is measured before and after the exposures. The concepts presented would lead to the new insights into proteins susceptibility to perturbation by exposure to electromagnetic fields and possibility to program, predict, design and modify proteins and their bioactivit

A Simple three-step method for design and affinity testing of new antisense peptides: an example of erythropoietin

Antisense peptide technology is a valuable tool for deriving new biologically active molecules and performing peptide–receptor modulation. It is based on the fact that peptides specified by the complementary (antisense) nucleotide sequences often bind to each other with a higher specificity and efficacy. We tested the validity of this concept on the example of human erythropoietin, a well-characterized and pharmacologically relevant hematopoietic growth factor. The purpose of the work was to present and test simple and efficient three-step procedure for the design of an antisense peptide targeting receptor-binding site of human erythropoietin. Firstly, we selected the carboxyl-terminal receptor binding region of the molecule (epitope) as a template for the antisense peptide modeling ; Secondly, we designed an antisense peptide using mRNA transcription of the epitope sequence in the 3'→5' direction and computational screening of potential paratope structures with BLAST ; Thirdly, we evaluated sense–antisense (epitope–paratope) peptide binding and affinity by means of fluorescence spectroscopy and microscale thermophoresis. Both methods showed similar Kd values of 850 and 816 µM, respectively. The advantages of the methods were: fast screening with a small quantity of the sample needed, and measurements done within the range of physicochemical parameters resembling physiological conditions. Antisense peptides targeting specific erythropoietin region(s) could be used for the development of new immunochemical methods. Selected antisense peptides with optimal affinity are potential lead compounds for the development of novel diagnostic substances, biopharmaceuticals and vaccines

Aerospace medicine and biology: A continuing bibliography with indexes

This bibliography lists 148 reports, articles and other documents introduced into the NASA scientific and technical information system in December 1984

The hippocampus and cerebellum in adaptively timed learning, recognition, and movement

The concepts of declarative memory and procedural memory have been used to distinguish two basic types of learning. A neural network model suggests how such memory processes work together as recognition learning, reinforcement learning, and sensory-motor learning take place during adaptive behaviors. To coordinate these processes, the hippocampal formation and cerebellum each contain circuits that learn to adaptively time their outputs. Within the model, hippocampal timing helps to maintain attention on motivationally salient goal objects during variable task-related delays, and cerebellar timing controls the release of conditioned responses. This property is part of the model's description of how cognitive-emotional interactions focus attention on motivationally valued cues, and how this process breaks down due to hippocampal ablation. The model suggests that the hippocampal mechanisms that help to rapidly draw attention to salient cues could prematurely release motor commands were not the release of these commands adaptively timed by the cerebellum. The model hippocampal system modulates cortical recognition learning without actually encoding the representational information that the cortex encodes. These properties avoid the difficulties faced by several models that propose a direct hippocampal role in recognition learning. Learning within the model hippocampal system controls adaptive timing and spatial orientation. Model properties hereby clarify how hippocampal ablations cause amnesic symptoms and difficulties with tasks which combine task delays, novelty detection, and attention towards goal objects amid distractions. When these model recognition, reinforcement, sensory-motor, and timing processes work together, they suggest how the brain can accomplish conditioning of multiple sensory events to delayed rewards, as during serial compound conditioning.Air Force Office of Scientific Research (F49620-92-J-0225, F49620-86-C-0037, 90-0128); Advanced Research Projects Agency (ONR N00014-92-J-4015); Office of Naval Research (N00014-91-J-4100, N00014-92-J-1309, N00014-92-J-1904); National Institute of Mental Health (MH-42900

Designer Gene Networks: Towards Fundamental Cellular Control

The engineered control of cellular function through the design of synthetic genetic networks is becoming plausible. Here we show how a naturally occurring network can be used as a parts list for artificial network design, and how model formulation leads to computational and analytical approaches relevant to nonlinear dynamics and statistical physics.Comment: 35 pages, 8 figure

Brains and Education: Towards Neurocognitive Phenomics

Phenomics is concerned with detailed description of all aspects of organisms, from their physical foundations at genetic, molecular and cellular level, to behavioural and psychological traits. Neuropsychiatric phenomics tries to understand mental disease from such broad perspective. It is clear that learning sciences also need similar approach that should integrate efforts to understand cognitive processes from the perspective of the brain development, in temporal, spatial, psychological and social aspects. A new branch of science called neurocognitive phenomics is proposed, treating the brain as a substrate shaped by the genetic, epigenetic, cellular and environmental factors, in which learning processes due to the individual experiences, social contacts, education and culture take place. A brief review of selected aspects, from genes to learning styles, is presented, and a link between central, peripheral and motor processes in the brain linked to learning styles