P > .05: The incorrect interpretation of “not significant” results is a significant problem

Statistically nonsignificant (p > .05) results from a null hypothesis significance test (NHST) are often mistakenly interpreted as evidence that the null hypothesis is true—that there is “no effect” or “no difference.” However, many of these results occur because the study had low statistical power to detect an effect. Power below 50% is common, in which case a result of no statistical significance is more likely to be incorrect than correct. The inference of “no effect” is not valid even if power is high. NHST assumes that the null hypothesis is true; p is the probability of the data under the assumption that there is no effect. A statistical test cannot confirm what it assumes. These incorrect statistical inferences could be eliminated if decisions based on p values were replaced by a biological evaluation of effect sizes and their confidence intervals. For a single study, the observed effect size is the best estimate of the population effect size, regardless of the p value. Unlike p values, confidence intervals provide information about the precision of the observed effect. In the biomedical and pharmacology literature, methods have been developed to evaluate whether effects are “equivalent,” rather than zero, as tested with NHST. These methods could be used by biological anthropologists to evaluate the presence or absence of meaningful biological effects. Most of what appears to be known about no difference or no effect between sexes, between populations, between treatments, and other circumstances in the biological anthropology literature is based on invalid statistical inference.     

Self organization origin of life scenarios and information theory

The self organizationist scenarios for the origin of life are examined by means of information theory. It is found that self organization must yield only genetic message ensembles of information content much too low to constitute a genome. It is shown that the statistical structure reflected in “the instructions in the amino acids themselves” is an impediment to the generation of genetic information not a source of it. It is concluded that at present there are no scientifically valid origin of life scenarios. Consequently, belief in little green men in outer space is purely religious not scientific.     

Are introns in-series error-detecting sequences?

The probability of the accurate transmission of a message sequence can be increased by the addition of non-message sequences which permit errors in the message sequence to be detected and corrected. It is proposed that sequences in introns (or in other non-message genomic regions) serve this function with respect to the transmission of genetic information.     

Unbiased vs. biased approaches to the identification of cancer signatures: the case of lung cancer

Expression profiling analysis of human cancers is a promising approach to obtain precise molecular classification of cancers, to develop stratification tools for therapeutic regimens, and to predict the biological behavior of neoplasia. Direct profiling of human cancers (herein defined as “the unbiased approach”) presents, however, intrinsic problems connected with the high genetic noise embedded in the system. This, in turn, leads to fitting of the noise in the data (the so-called “overtraining”) with consequent instability of the identified signatures, when applied on different cohorts of patients. To circumvent these problems, “biased approaches” - which exploit the molecular knowledge of cancer obtained in model systems - are being developed. Biased approaches, however, are not problem-free, in that they provide information limited to single oncogenic events, thereby failing, at least in principle, to capture the complex repertoire of alterations of human cancers. In this review, we compare the two approaches and provide a test case, from our studies, of how “integrated” strategies, which combine biased and unbiased approaches, might lead to the identification of stable and reliable predictive signatures in cancer.     

The accuracy of Bartlett's small-fluctuation approximation for stochastic-difference-equation population models

A heuristic approximation procedure devised by Bartlett has often been used to estimate the stationary first- and second-order moments of difference-equation population models perturbed by “small” noise. Here, the approximation is proved to be valid under quite general assumptions: the exact and approximate moments differ by an amount of order σ³ as σ → 0, where σ² is the mean-square norm of the noise process. The existence of stationary solutions to the perturbed difference equation is also considered. If the noise is Markovian, stationary solutions satisfying the assumptions of the error analysis are proved to exist if the noise is “small” with probability 1. The results are applied to a population model with two age classes and variable recruitment.     

A simple first-principles model of reduplication

From first principles, a simple model was derived to describe the reduplication of the molecular structure as a sequence of stages whose probabilities can be estimated using the general theory of molecular transformations. It was shown that the genetic information transfer in time (the phenomenon of life) for a long period is impossible without simultaneous “phenomenon of death” and that taking into account the features of transition states in reactions (quantum beats) leads to self-oscillations.     

On the origin of the genetic code and the stability of the translation apparatus

An “error theory” is developed which can be applied to determine the stability of a macromolecular translation machinery which reproduces itself. It is shown that the overall effects of a multitude of possible error versions of macromolecules can be treated statistically, and that such a statistical approach is of considerable usefulness in the theoretical treatment of complex macromolecular systems. The theory is developed within the context of a detailed treatment of the “frozen accident” hypothesis for the origin of the genetic code. A model is described which permits some thermodynamic characterization of the components involved in the code nucleation. The model also proves useful in resolving a stability “paradox” described by Orgel, which relates to the translation stability in present-day organisms and mechanisms of ageing. It indicates that any experimentally found decrease in translation accuracy with age is probably not due to an inherent instability in the translation apparatus. Relevant experiments are suggested.     

Second Moscow Conference on Computational Molecular Biology MCCMB’05

From first principles, a simple model was derived to describe the reduplication of the molecular structure as a sequence of stages whose probabilities can be estimated using the general theory of molecular transformations. It was shown that the genetic information transfer in time (the phenomenon of life) for a long period is impossible without simultaneous “phenomenon of death” and that taking into account the features of transition states in reactions (quantum beats) leads to self-oscillations.     

A calculation of the probability of spontaneous biogenesis by information theory.

The Darwin-Oparin-Haldane “warm little pond” scenario for biogenesis is examined by using information theory to calculate the probability that an informational biomolecule of reasonable biochemical specificity, long enough to provide a genome for the “protobiont”, could have appeared in 10⁹ years in the primitive soup. Certain old untenable ideas have served only to confuse the solution of the problem. Negentropy is not a concept because entropy cannot be negative. The role that negentropy has played in previous discussions is replaced by “complexity” as defined in information theory. A satisfactory scenario for spontaneous biogenesis requires the generation of “complexity” not “order”. Previous calculations based on simple combinatorial analysis over estimate the number of sequences by a factor of 10⁵. The number of cytochrome c sequences is about 3·8 × 10⁶¹. The probability of selecting one such sequence at random is about 2·1 ×10^?65. The primitive milieu will contain a racemic mixture of the biological amino acids and also many analogues and non-biological amino acids. Taking into account only the effect of the racemic mixture the longest genome which could be expected with 95 % confidence in 10⁹ years corresponds to only 49 amino acid residues. This is much too short to code a living system so evolution to higher forms could not get started. Geological evidence for the “warm little pond” is missing. It is concluded that belief in currently accepted scenarios of spontaneous biogenesis is based on faith, contrary to conventional wisdom.     

The impact of under and over-recording of cancer on death certificates in a competing risks analysis: A simulation study

Background: With linked register and cause of death data becoming more accessible than ever, competing risks methodology is being increasingly used as a way of obtaining “real world” probabilities of death broken down by specific causes. It is important, in terms of the validity of these studies, to have accurate cause of death information. However, it is well documented that cause of death information taken from death certificates is often lacking in accuracy and completeness. Methods: We assess through use of a simulation study the effect of under and over-recording of cancer on death certificates in a competing risks analysis consisting of three competing causes of death: cancer, heart disease and other causes. Using realistic levels of misclassification, we consider 24 scenarios and examine the bias in the cause-specific hazard ratios and the cumulative incidence function. Results: The bias in the cumulative incidence function was highest in the oldest age group reaching values as high as 2.6 percentage units for the “good” cancer prognosis scenario and 9.7 percentage units for the “poor” prognosis scenario. Conclusion: The bias resulting from the chosen levels of misclassification in this study accentuate concerns that unreliable cause of death information may be providing misleading results. The results of this simulation study convey an important message to applied epidemiological researchers.     

Bayesian image restoration models for combining expert knowledge on recording activity with species distribution data

Biological atlases are, for many species, the only source of information on their distribution over large geographical areas, and are widely used to inform models of the environmental distribution of species. Such data are not collected using standardized survey techniques, however, and spatial variations in coverage (the relative extent or completeness of records) may lead to variations in the probability that the species will be recorded at locations where it is present (the “recording probability”). If spatial patterns in recording probabilities are correlated with key environmental variables, then biased estimates of the relationships between environmental variables and species distributions may be obtained. We outline a general statistical framework for modelling the environmental distribution of species using, known as Bayesian Image Restoration (BIR). BIR can be used in combination with any species distribution model, but in addition allows us to account for spatial heterogeneity in recording probabilities by utilizing expert knowledge on spatial patterns in coverage. We illustrate the methodology by applying it to maps of the recorded distribution of two plant species in Germany, taken from the German atlas of vascular plants. We find that estimated spatial patterns in recording probabilities for both species are correlated with key environmental variables. Consequently, different relationships between the probability of presence of a species and environmental variables were obtained when the species distribution models were parameterised within a BIR framework. Care must be taken in the application of BIR, since the resulting inferences can depend strongly upon the modelling assumptions that are adopted. Nevertheless, we conclude that BIR has the potential to make better use of uncertain information on species distributions than conventional methods, and can be used to formally investigate the robustness of inferences on the environmental distribution of species to assumptions concerning spatial patterns in recording probabilities.     

Qualitative information and comparative informativeness

This paper pursues three basic definitions of comparative information motivated by various theories of information. The first definition involves the ordering of experiments according to a qualitative relation “not more informative than”, the second is derived from measure-theoretic properties of information without probability leading to a construction of a partially ordered algebra of information, the third is based on a particular aspect of qualitative semantic information involving the ordering of propositions according to their information content. This approach leads to a Boolean interpretation of informative propositions generating a qualitative probability structure. Some ways are discussed how to represent informative propositions by compatible normed information measures, leading to a measure of probability in terms of information.     

Certain Non-Standard Coding Tables Appear to be More Robust to Error Than the Standard Genetic Code

Since the identification of the Standard Coding Table as a “universal” method to translate genetic information into amino acids, exceptions to this rule have been reported, and to date there are nearly 20 alternative genetic coding tables deployed by either nuclear genomes or organelles of organisms. Why are these codes still in use and why are new codon reassignments occurring? This present study aims to provide a new method to address these questions and to analyze whether these alternative codes present any advantages or disadvantages to the organisms or organelles in terms of robustness to error. We show that two of the alternative coding tables, The Ciliate, Dasycladacean and Hexamita Nuclear Code (CDH) and The Flatworm Mitochondrial Code (FMC), exhibit an advantage, while others such as The Yeast Mitochondrial Code (YMC) are at a significant disadvantage. We propose that the Standard Code is likely to have emerged as a “local minimum” and that the “coding landscape” is still being searched for a “global” minimum.     

Errors and Their Mitigation at the Kirchhoff-Law-Johnson-Noise Secure Key Exchange

A method to quantify the error probability at the Kirchhoff-law-Johnson-noise (KLJN) secure key exchange is introduced. The types of errors due to statistical inaccuracies in noise voltage measurements are classified and the error probability is calculated. The most interesting finding is that the error probability decays exponentially with the duration of the time window of single bit exchange. The results indicate that it is feasible to have so small error probabilities of the exchanged bits that error correction algorithms are not required. The results are demonstrated with practical considerations.     

不同地理种群银杏大蚕蛾COI基因序列变异与遗传分化

银杏大蚕蛾Caligula japonica是亚洲东部的特有种, 既是一种重要的林业害虫, 也是一种珍贵的野生蚕类资源。为了揭示银杏大蚕蛾地理种群间的内在联系, 测定了我国分布的12个地理种群的线粒体细胞色素氧化酶C亚基I（COI）基因部分序列（GenBank登录号: FJ358506-FJ358517）, 对地理种群间的序列变异和遗传分化进行了分析。结果表明: 银杏大蚕蛾地理种群间的COI序列同源性高达99%~100%, 显示出比较小的遗传差异。序列对准后从供试COI序列中仅鉴定出9个变异位点和6个单元型, 其中3种是共享单元型。系统发育分析结果表明种群间已经按地理位置形成了一定的地理格局, AMOVA分析显示北方组和南方组之间已经具有明显的遗传分化（FST=0.478, P<0.001）。综合分析, 我们认为北方组和南方组之间的遗传分化可能与差异巨大的生态条件有关。研究结果为银杏大蚕蛾的种群遗传学和生态学研究提供了一个基本的分子生物学线索。     

Extracting abundance information from DNA-based data

The accurate extraction of species-abundance information from DNA-based data (metabarcoding, metagenomics) could contribute usefully to diet analysis and food-web reconstruction, the inference of species interactions, the modelling of population dynamics and species distributions, the biomonitoring of environmental state and change, and the inference of false positives and negatives. However, multiple sources of bias and noise in sampling and processing combine to inject error into DNA-based data sets. To understand how to extract abundance information, it is useful to distinguish two concepts. (i) Within-sample across-species quantification describes relative species abundances in one sample. (ii) Across-sample within-species quantification describes how the abundance of each individual species varies from sample to sample, such as over a time series, an environmental gradient or different experimental treatments. First, we review the literature on methods to recover across-species abundance information (by removing what we call “species pipeline biases”) and within-species abundance information (by removing what we call “pipeline noise”). We argue that many ecological questions can be answered with just within-species quantification, and we therefore demonstrate how to use a “DNA spike-in” to correct for pipeline noise and recover within-species abundance information. We also introduce a model-based estimator that can be used on data sets without a physical spike-in to approximate and correct for pipeline noise.     

Which aging in yeast is “true”?

Two model systems, “replicative aging” and “chronological aging” (CA), which are used for gerontological research on the yeast Saccharomyces cerevisiae, are compared. In the first case, the number of daughter cells generated by an individual mother cell before cell propagation irreversibly stops is analyzed. This makes the model very similar to the well-known Hayflick model. In the case of CA, the survival of yeast cell population in the stationary phase of growth is studied. It is noted that the second model is similar to the “stationary phase aging” model, which is used in the author’s laboratory for cytogerontological studies on animal and human cells. It is assumed that the concept of cell proliferation restriction as the main cause of age-related accumulation in the cells of multicellular organisms of macromolecular defects (primarily DNA damage) leading to deterioration of tissue and organ functioning and, as a result, to an increase in the death probability allows explaining how the aging process proceeds in almost any living organisms. Apparently, in all cases, this process is initiated by the appearance of slow propagating (or not propagating at all) cells, which leads to the termination of “dilution,” with the help of new cells, of macromolecular defects accumulating at the level of whole cell population. It is concluded that data on the geropromoter or geroprotector activity of various factors obtained in tests on the yeast CA model can be used with a high reliability to understand the mechanisms of human aging and longevity.