[The auto-antibodies. 3. The mechanism of antibody production. Classical theory (information theory)].
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Information theory-based software tools have been useful in interpreting noncoding sequence variation within functional sequence elements such as splice sites. Individual information analysis detects activated cryptic splice sites and associated splicing regulatory sites and is capable of distinguishing null from partially functional alleles. We present a server (https://splice.cmh.edu) designed to analyze splicing mutations in binding sites in either human genes, genome-mapped mRNAs, user-defined sequences, or dbSNP entries. Standard HUGO-approved gene symbols and HGVS-approved systematic mutation nomenclature (or dbSNP format) are entered via a web portal. After verifying the accuracy of input variant(s), the surrounding interval is retrieved from the human genome or user-supplied reference sequence. The server then computes the information contents (Ri) of all potential constitutive and/or regulatory splice sites in both the reference and variant sequences. Changes in information content are color-coded, tabulated, and visualized as sequence walkers, which display the binding sites with the reference sequence. The software was validated by analyzing approximately 1,300 mutations from Human Mutation as well as eight mapped SNPs from dbSNP designated as splice site variants. All of the splicing mutations and variants affected splice site strength or activated cryptic splice sites. The server also detected several missense mutations that were unexpectedly predicted to have concomitant effects on splicing or appeared to activate cryptic splicing.
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Using information theory, a model communication channel has been constructed to assess the information gain from the performance of clinical chemical tests, in particular qualitative tests. The construct of the model communication channel is especially clear, and it can be easily adapted to the most varied clinical enquiries. The information theoretical parameters, transinformation and test capacity, are used to characterize the information properties of a clinical chemical test. The calculations necessary for the practical application can (primarily when matrices are used) be performed without difficulty, even by non-mathematicians, using modern table calculators. The procedure is illustrated with many numerical examples, and especially applied to combination of qualitative tests.
An information theory approach was developed to predict the alignment of interacting antiparallel and parallel beta-strands. Information scores were derived for the preference of a residue on a beta-strand to be opposite a sequence of residues on an adjacent beta-strand. These scores were used to predict the interstrand register of interacting beta-strands from 10 alternative offset positions either side of the experimentally observed beta-sheet register. The amino acid sequence of an internal beta-strand can be correctly aligned with two beta-strands in a fixed position either side of the strand in 45% of antiparallel and 48% of parallel arrangements. For comparison, when another beta-strand from a nonhomologous protein substitutes the internal beta-strand, the same register is predicted for only 24 and 36% of antiparallel and parallel arrangements. As expected, alignment of a single fixed strand with just a second beta-strand sequence was more difficult, and gave a correct register in 31 and 37% of antiparallel and parallel beta-pairs, respectively. These scores are 10% higher than for two randomly selected beta-strand sequences. In general, prediction accuracy was not improved by information tables that distinguished hydrogen-bonding patterns or beta-strand order. These results will contribute to predicting the arrangement of beta-strands in beta-pleated sheets and protein topology.
Cellular information dynamics during somatic evolution of the malignant phenotypes are complex and poorly understood. Accumulating, random genetic mutations and, therefore, loss of genomic information appears necessary for carcinogenesis. However, additional control parameters can be inferred because unconstrained mutagenesis would ultimately produce cellular information degradation incompatible with life. Similarly, the stability of some genomic segments, such as those controlling proliferation and metabolism, indicates the presence of selective mutational constraints. By applying Information Theory and Extreme Physical Information (EPI) analysis, we demonstrate that the phenotypic characteristics and growth pattern of cancer populations are emergent properties resulting from the nonlinear dynamics of accumulating, random genetic mutations and tissue selection factors. Maximum quantitative loss of transgenerational information is demonstrated in genomic segments encoding negative or neutral evolutionary properties. This is most evident in the progressive dedifferentiation observed during carcinogenesis and may terminate in a differentiation "information catastrophe" producing decoherent cellular morphology and function. In contrast, microenvironmental selection pressures preserve genomic information controlling properties that confer selective growth advantages even in the presence of a high background mutation rate. Thus, phenotypic traits characteristically retained by tumor populations can be identified as critical selection parameters favoring clonal proliferation. The information model of carcinogenesis is tested by applying EPI analysis to predict tumor growth dynamics. We found that cellular proliferation attributable to information degradation will produce power law tumor growth with an exponent of 1.62. Data from six published studies that use sequential mammograms to measure the volume of small, untreated human breast cancers demonstrate power law tumor growth with a mean exponent value of 1.73 +/- 0.23. Other predictions including exponential growth of tumor cells in vitro are also supported by experimental observations. The nonlinear dynamics of stochastic information loss constrained by somatic evolution indicate that carcinogenesis will not be associated with any predictable, fixed sequence of genomic alterations. Rather, sporadic clinical cancers are emergent structures produced by multiple, fundamentally nondeterministic genetic pathways.
We generalize Shannon's information theory in a nonadditive way by focusing on the source coding theorem. The nonadditive information content we adopted is consistent with the concept of the form invariance structure of the nonextensive entropy. Some general properties of the nonadditive information entropy are studied, in addition, the relation between the nonadditivity q and the codeword length is pointed out.
Information theory quantifies how much information a neural response carries about the stimulus. This can be compared to the information transferred in particular models of the stimulus-response function and to maximum possible information transfer. Such comparisons are crucial because they validate assumptions present in any neurophysiological analysis. Here we review information-theory basics before demonstrating its use in neural coding. We show how to use information theory to validate simple stimulus-response models of neural coding of dynamic stimuli. Because these models require specification of spike timing precision, they can reveal which time scales contain information in neural coding. This approach shows that dynamic stimuli can be encoded efficiently by single neurons and that each spike contributes to information transmission. We argue, however, that the data obtained so far do not suggest a temporal code, in which the placement of spikes relative to each other yields additional information.
This paper examines the application of Information Theory to hospital discharge data. Information Theory offers a general methodology to compare sets of casemix proportions as a measure of (1) the concentration of admissions across hospitals for specific medical conditions and (2) specialization across diagnostic categories for individual hospitals. Unfortunately, Information Theory indices are difficult to interpret and subject to a potentially serious statistical bias when computed from discrete frequency counts, such as those obtained from discharge abstract data. The analysis presented here first clarifies the interpretation of Information Theory indices by relating them to formal statistical tests of hypotheses about hospital and diagnosis-specific patterns of admissions. It then documents the magnitude of the bias due to calculating indices from discrete frequency counts and proposes analytical strategies for dealing with this bias. Finally, the paper examines the empirical importance of the bias and the proposed adjustment, using data that are typical of those available for research on hospital casemix.
OBJECTIVE: We examine the use of information theory applied to a single cardiac troponin T (cTnT) (first generation monoclonal; Boehringer Mannheim Corp., Indianapolis, Indiana) used with the character of chest pain, electrocardiography (ECG) and serial ECG changes in the evaluation of acute myocardial infarction (AMI). We combined a single measure of cTnT (blinded to the investigators) with a creatine kinase MB isoenzyme (CK-MB) measurement to discover the best decision value for this test in a study of 293 consecutive patients presenting to the emergency department with symptoms warranting exclusion of AMI. METHODS: The decision value for determining whether cTnT is positive or negative was determined independently of the final diagnosis by examining the information in the cTnT and CKMB data. Using information theory, an autocorrelation matrix with a one-to-one pairing of the CKMB and troponin T was constructed. The effective information, also known as Kullback entropy, assigned the values for troponin T and for CKMB that have the lowest frequency of misclassification error. The Kullback entropy is determined by subtracting the data entropy from the maximum entropy of the data set in which the information has been destroyed. The assignment of the optimum decision values was made independently of the clinical diagnoses without the construction of a receiver-operator characteristic curve (ROC). The final diagnosis of AMI was independently determined by the clinicians and entered into the medical record. RESULTS: The decision value for cTnT was 0.1 ng/ml as determined by the the information in the data. The method was validated within the same study by mapping the results so obtained into the diagnoses obtained independently by the clinicians using all of the methods at their disposal. The cTnT was different in AMI (n = 60) compared with non-AMI patients (n = 233) (2.08 +/- 0.21 vs. 0.07 +/- 0.10; p < .0001). CONCLUSION: Information theory provides a strong framework and methodology for determining the decision value for cTnT which minimizes misclassification errors at 0.1 ng/ml. The result has a strong correlation with other features in detecting AMI in patients presenting with chest pain.
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Application of the general theory of information and of communication to auditory function enables the internal ear to be assimilated to a digital-analog converter capable of coding the continuous acoustic signal into discontinuous, impulsional type nervous signals. In this model, the ear selects spatio temporal samples of membranous acoustic forms, discrimination of intensity devolving upon the external ciliated system and that of the height upon the internal ciliated system. It allows simple correlation of apparently paradoxical psycho-acoustic phenomena with objective acoustic or histopathological data.
The concepts of information theory were applied to the high-performance liquid chromatography (HPLC) technique, with diode-array (DAD) and/or fluorescence (FLD) detections. The information amount for a complete analysis can be computed as a function of analytical parameters, such as the number of analytes, level of concentration, and standard deviation of determinations. By means of the proposed method, the information content of a qualitative and quantitative analysis accomplished by HPLC-DAD-FLD was estimated, and sensitivity was optimized taking into account a maximum information content, while the detection limit was estimated considering that at this level of concentration the information content approaches zero.
During the search for new structural descriptors we have defined the information-theory operators U(M), V(M), X(M), and Y(M), that are computed from atomic invariants and measure the information content of the elements of molecular matrices. Structural descriptors computed with these four information-theory operators are used to develop structure-property models for the boiling temperature, molar heat capacity, standard Gibbs energy of formation, vaporization enthalpy, refractive index, and density of alkanes. The information-theory operators were applied to six molecular matrices, namely, the distance D, the reciprocal distance RD, the distance-path Dp, the reciprocal distance-path RDp, the path Szeged Sz(p), and the reciprocal path Szeged RSz(p) matrices. In combination with other topological indices, the information-theory indices offer good structure-property models for all six alkane properties investigated in this study.
Performance in sensory discrimination tasks is commonly quantified using either information theory or ideal observer analysis. These two quantitative frameworks are often assumed to be equivalent. For example, higher mutual information is said to correspond to improved performance of an ideal observer in a stimulus estimation task. To the contrary, drawing on and extending previous results, we show that five information-theoretic quantities (entropy, response-conditional entropy, specific information, equivocation, and mutual information) violate this assumption. More positively, we show how these information measures can be used to calculate upper and lower bounds on ideal observer performance, and vice versa. The results show that the mathematical resources of ideal observer analysis are preferable to information theory for evaluating performance in a stimulus discrimination task. We also discuss the applicability of information theory to questions that ideal observer analysis cannot address.
Comparative analysis of nonhuman animal communication systems and their complexity, particularly in comparison to human language, has been generally hampered by both a lack of sufficiently extensive data sets and appropriate analytic tools. Information theory measures provide an important quantitative tool for examining and comparing communication systems across species. In this paper we use the original application of information theory, that of statistical examination of a communication system's structure and organization. As an example of the utility of information theory to the analysis of animal communication systems, we applied a series of information theory statistics to a statistically categorized set of bottlenose dolphin Tursiops truncatus, whistle vocalizations. First, we use the first-order entropic relation in a Zipf-type diagram (Zipf 1949 Human Behavior and the Principle of Least Effort) to illustrate the application of temporal statistics as comparative indicators of repertoire complexity, and as possible predictive indicators of acquisition/learning in animal vocal repertoires. Second, we illustrate the need for more extensive temporal data sets when examining the higher entropic orders, indicative of higher levels of internal informational structure, of such vocalizations, which could begin to allow the statistical reconstruction of repertoire organization. Third, we propose using 'communication capacity' as a measure of the degree of temporal structure and complexity of statistical correlation, represented by the values of entropic order, as an objective tool for interspecies comparison of communication complexity. In doing so, we introduce a new comparative measure, the slope of Shannon entropies, and illustrate how it potentially can be used to compare the organizational complexity of vocal repertoires across a diversity of species. Finally, we illustrate the nature and predictive application of these higher-order entropies using a preliminary sample of dolphin whistle vocalizations. The purpose of this preliminary report is to re-examine the original application of information theory to the field of animal communication, illustrate its potential utility as a comparative tool for examining the internal informational structure of animal vocal repertoires and their development, and discuss its relationship to behavioural ecology and evolutionary theory. Copyright 1999 The Association for the Study of Animal Behaviour.