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PubMed1975

The neonate's immunity gap, breast feeding and cot death.

In many mammals infant behaviour imposes a period during which the young will only take the mother's milk. It is suggested that the immunological components of the milk serve in this period to augment the baby's immune system while he traverses from the antigenic isolation of a fetus to his independent defence. In humans almost all cot deaths occur during this phase. Diverse statistics relating to factors associated with greater risk of cot death are drawn on, suggesting that a number of seemingly unconnected factors can all (including lack of breast-feeding) be interpreted as potential immunity defaults. This interpretation lends support to the idea of an immune mechanism underlying cot death which in some way is an abnormal response resulting from the default and which, with at least one other precipitating mechanism, leads to death.

Anaphylaxis↗
PubMed2026

MultiDMPcaller: a one-stop software for detection and visualization of differentially methylated positions and regions.

MOTIVATION: Whole-genome bisulfite sequencing (WGBS/BS-Seq) is the gold standard for single-base resolution DNA methylome profiling. However, the diverse statistical models of existing computational methods lead to limited overlap between their results, highlighting the need for novel methods to detect differentially methylated positions (DMPs) and differentially methylated regions (DMRs). RESULTS: We developed MultiDMPcaller, an automated downstream methylome analysis software. It processes upstream outputs to profile DMPs, non-DMPs, DMRs, and context-specific (CpG/CHG/CHH) methylation status, alongside visualizing their chromosomal distribution and enrichment. The software features two key innovations: (i) an adaptive two-step P-value adjustment strategy based on organism-specific methylation patterns, with raw P-value ≤0.05 pre-filtering followed by false discovery rate (FDR) correction, to recover potential DMPs usually missed by standard FDR correction in plant CHG/CHH and animal CpG contexts; and (ii) a multiple pairwise comparison approach, which performs m × n pairwise comparisons for m control and n experimental replicates, followed by a voting system supporting both user-defined majority thresholds and model-based adaptive thresholds, to identify robust and reliable DMPs (with a stricter voting threshold exclusively for loci with low methylation differences) and DMRs. On real datasets from Arabidopsis, apple, and mouse, as well as simulated human datasets, MultiDMPcaller's results showed good agreement with those of other software, exhibiting high conservativeness and superior precision, which suggested a low false discovery proportion. AVAILABILITY AND IMPLEMENTATION: MultiDMPcaller is available at GitHub (https://github.com/jiantaoyuNWAFU/MultiDMPcaller) and via a web server (https://ciebioinfo.nwafu.edu.cn).

Software↗
PubMed1991

Length and sequence variation in evening bat D-loop mtDNA.

Length variation in D-loop mitochondrial DNA was observed after amplification with the polymerase chain reaction (PCR) in 28% of 195 evening bats, Nycticeius humeralis, from seven colonies. Nucleotide sequences of PCR products show that this heteroplasmy is characterized by an 81-bp region which is tandemly repeated five to eight times. Southern blots using PCR products as probes on HaeIII genomic digests confirm the presence of heteroplasmy. Furthermore, densitometry of electrophoresed PCR products from 109 mother-offspring pairs indicate that heteroplasmy is stably transmitted from mother to offspring with one exception: a heteroplasmic offspring had a homoplastic mother and sib. Nucleotide sequences from this family reveal that a repeat duplication and deletion occurred. The observed mutation rate per generation, mu, for length polymorphism is comparable to an independent estimate, mu = 10(-2), based on hierarchical diversity statistics. With the exception of the repeat nearest the proline tRNA gene, sequence similarities between repeats within bats are consistent with a model of concerted evolution due to unidirectional replication slippage. Selection is inferred to act on the first repeat because in comparison to other repeats it has the least sequence divergence among bats, the fewest transversions, and the lowest minimum free energy associated with folding.

Animals↗
PubMed1996

Hierarchical analysis of nucleotide diversity in geographically structured populations.

Existing methods for analyzing nucleotide diversity require investigators to identify relevant hierarchical levels before beginning the analysis. We describe a method that partitions diversity into hierarchical components while allowing any structure present in the data to emerge naturally. We present an unbiased version of NEI's nucleotide diversity statistics and show that our modification has the same properties as WRIGHT's FST. We compare its statistical properties with several other FST estimators, and we describe how to use these statistics to produce a rooted tree of relationships among the sampled populations in which the mean time to coalescence of haplotypes drawn from populations belonging to the same node is smaller than the mean time to coalescence of haplotypes drawn from populations belonging to different nodes. We illustrate the method by applying it to data from a recent survey of restriction site variation in the chloroplast genome of Coreopsis grandiflora.

Chloroplasts↗
PubMed2003

Diet influences the ecology of lactic acid bacteria and Escherichia coli along the digestive tract of cattle: neural networks and 16S rDNA.

In this manuscript, the authors have sought to gain a better understanding of the interactions between Escherichia coli and lactic acid bacteria (LAB) isolated from Rogossa MRS agar along the digestive tract of grain- and forage-fed cattle. E. coli from cattle receiving a high-grain diet were more numerous (P<0.05) than from the high-forage diet and the highest numbers were in the faeces. Isolates on Rogossa MRS agar were always greater in the high-grain diet (P<0.05) and contained a significant number of LAB. A random set of Rogossa MRS agar colonies was selected and artificial neural networks were used to develop a relationship between colony description and species which was validated using sequence analysis (16S rDNA). The neural networks correctly predicted species in more than 80 % of cases and was composed, primarily, of Lactobacillus vitulinus, Lactobacillus ruminis, Selenomonas ruminantium, Streptococcus bovis, Acidaminococcus fermentans and Megasphaera elsdenii. In conjunction with statistical diversity indices, it was demonstrated that diversity in the high-fibre diet was always lower and was a consequence of the dominance of Str. bovis. In contrast, the diversity in the high-grain diet was greater (P<0.05) and was a consequence of the decline in Str. bovis. These data demonstrate that there is a positive relationship between coliform and LAB isolates throughout the digestive tract of cattle, and diet is the major factor regulating bacterial composition.

Animal Feed↗
PubMedDate not supplied

A methodology for validating numerical ground water models.

Ground water validation is one of the most challenging issues facing modelers and hydrogeologists. Increased complexity in ground water models has created a gap between model predictions and the ability to validate or build confidence in predictions. Specific procedures and tests that can be easily adapted and applied to determine the validity of site-specific ground water models do not exist. This is true for both deterministic and stochastic models, with stochastic models posing the more difficult validation problem. The objective of this paper is to propose a general validation approach that addresses important issues recognized in previous validation studies, conferences, and symposia. The proposed method links the processes for building, calibrating, evaluating, and validating models in an iterative loop. The approach focuses on using collected validation data to reduce uncertainty in the model and narrow the range of possible outcomes. This method is designed for stochastic numerical models utilizing Monte Carlo simulation approaches, but it can be easily adapted for deterministic models. The proposed methodology relies on the premise that absolute validity is not theoretically possible, nor is it a regulatory requirement. Rather, the proposed methodology highlights the importance of testing various aspects of the model and using diverse statistical tools for rigorous checking and confidence building in the model and its predictions. It is this confidence that will encourage regulators and the public to accept decisions based on the model predictions. This validation approach will be applied to a model, described in this paper, dealing with an underground nuclear test site in rural Nevada.

Environmental Monitoring↗
PubMed2006

Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular evolution and population genetics.

BACKGROUND: A large number of bioinformatics applications in the fields of bio-sequence analysis, molecular evolution and population genetics typically share input/output methods, data storage requirements and data analysis algorithms. Such common features may be conveniently bundled into re-usable libraries, which enable the rapid development of new methods and robust applications. RESULTS: We present Bio++, a set of Object Oriented libraries written in C++. Available components include classes for data storage and handling (nucleotide/amino-acid/codon sequences, trees, distance matrices, population genetics datasets), various input/output formats, basic sequence manipulation (concatenation, transcription, translation, etc.), phylogenetic analysis (maximum parsimony, markov models, distance methods, likelihood computation and maximization), population genetics/genomics (diversity statistics, neutrality tests, various multi-locus analyses) and various algorithms for numerical calculus. CONCLUSION: Implementation of methods aims at being both efficient and user-friendly. A special concern was given to the library design to enable easy extension and new methods development. We defined a general hierarchy of classes that allow the developer to implement its own algorithms while remaining compatible with the rest of the libraries. Bio++ source code is distributed free of charge under the CeCILL general public licence from its website http://kimura.univ-montp2.fr/BioPP.

Algorithms↗
PubMed2002

Response of liver and heart trace elements in rats to the interaction between dietary zinc and iron.

An analysis of the interaction between dietary iron (Fe) and zinc (Zn) was performed by using data from Sprague-Dawley rats in a 5 x 4 fully crossed factorially arranged experiment. The concentrations of 9 trace elements from the liver and 10 from the heart were determined and subjected to diverse statistical analyses and were classified by their response to the interaction between dietary Fe and Zn. The interaction was studied by using analysis of variance (ANOVA), discriminant analysis, and logistic regression to determine the direction of interaction; that is, did dietary Fe affect dietary Zn or did dietary Zn affect dietary Fe? The use of discriminant analysis allowed for using multiple parameters (rather than a single parameter) to determine possible interactions between Fe and Zn. Thus, two main levels of interaction were studied: the separate response of each tissue mineral and the response of some grouped minerals. The responses studied were the effect of dietary Zn on tissue trace element parameters, the effect of dietary Fe on the parameters, the effect of dietary Zn on combined (grouped) parameters, and the effect of dietary Fe on combined parameters. As determined by ANOVA, only three individual trace elements--liver Fe, Cu, and Mo--were significantly affected by the interaction between Fe and Zn. However, a broader interaction between Fe and Zn is revealed when groups of, rather than single, trace elements arestudied. For example, an interaction between dietary Fe and Zn affects the weighted linear combination of heart Ca, Cu, K, Mg, Mn, P, and Zn. This article presents the hypothesis that grouped parameters may be useful as status indicators. The complete dataset can be found at http://www.gfhnrc.ars. usda.gov/fezn.

Analysis of Variance↗
PubMed2005

Statistics of infections with diversity in the pathogenicity.

The statistics of outbreaks in a model for the propagation of meningococcal disease is analyzed, taking into account the possibility that the population is fragmented into weakly connected patches. It is shown that, depending on the size of the sample studied, the ration between the variance and the average of infected cases can vary from unity (Poisson statistics) to epsilon(-1), where epsilon is the normalized infection rate.

Disease Outbreaks↗
PubMedDate not supplied

Boosted leave-many-out cross-validation: the effect of training and test set diversity on PLS statistics.

It is becoming increasingly common in quantitative structure/activity relationship (QSAR) analyses to use external test sets to evaluate the likely stability and predictivity of the models obtained. In some cases, such as those involving variable selection, an internal test set--i.e., a cross-validation set--is also used. Care is sometimes taken to ensure that the subsets used exhibit response and/or property distributions similar to those of the data set as a whole, but more often the individual observations are simply assigned 'at random.' In the special case of MLR without variable selection, it can be analytically demonstrated that this strategy is inferior to others. Most particularly, D-optimal design performs better if the form of the regression equation is known and the variables involved are well behaved. This report introduces an alternative, non-parametric approach termed 'boosted leave-many-out' (boosted LMO) cross-validation. In this method, relatively small training sets are chosen by applying optimizable k-dissimilarity selection (OptiSim) using a small subsample size (k = 4, in this case), with the unselected observations being reserved as a test set for the corresponding reduced model. Predictive errors for the full model are then estimated by aggregating results over several such analyses. The countervailing effects of training and test set size, diversity, and representativeness on PLS model statistics are described for CoMFA analysis of a large data set of COX2 inhibitors.

Algorithms↗
PubMed2001

Use of frequency diversity and Nakagami statistics in ultrasonic tissue characterization.

The Nakagami distribution was recently proposed as a generalized model for the envelope of the backscattered ultrasonic echo from tissue. The parameters of the Nakagami model were also shown to be useful in tissue characterization. This paper explores the possibility of enhancing the ability of these parameters for tissue characterization through the techniques of diversity and compounding. Frequency diversity has been used to create multiple versions of the envelope, which are then combined. This compounded envelope has been modeled, and its parameters have been analyzed. The ability of these new parameters to enhance tissue characterization is studied using computer simulation and experiments on tissue-mimicking phantoms. Results indicate that the use of frequency diversity and compounding may indeed improve the ability of the parameters of the Nakagami model to separate different number densities of scatterers. Therefore, it is suggested that such an approach may lead to better techniques in ultrasonic tissue characterization.

Biomedical Engineering↗
PubMed2002

Classification of ultrasonic B mode images of the breast using frequency diversity and Nakagami statistics.

The parameters of the Nakagami distribution have been utilized in the past to classify lesions in breast tissue as benign or malignant. To avoid the effect of operatorgain settings on the parameters of the Nakagami distribution, normalized parameters were utilized for the classification. The normalized parameter was defined as the ratio of the parameter at the site of the lesion to its average value over several regions away from the site. This technique, however, was very time consuming. In this paper, the application of frequency diversity and compounding is explored to achieve this normalization. Lesions are classified using these normalized parameters at the site. A receiver operating characteristic (ROC) analysis of the parameters of the Nakagami distribution has been conducted before and after compounding on a data set of 60 benign and 65 malignant lesions. The ROC results indicate that this technique can reasonably classify lesions in breast tissue as benign or malignant.

Biopsy↗
PubMed1977

F-statistics and analysis of gene diversity in subdivided populations.

It is show that Wright's F-statistics can be defined as ratios of gene diversities of heterozygosities rather than as the correlations of uniting gametes. This definition is applicable irrespective of the number of alleles involved or whether there is selection or not. The relationship between F-statistics and Nei's gene diversity analysis is discussed.

Alleles↗
PubMed2006

Statistical methods for characterizing diversity of microbial communities by analysis of terminal restriction fragment length polymorphisms of 16S rRNA genes.

The analysis of terminal restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes has proven to be a facile means to compare microbial communities and presumptively identify abundant members. The method provides data that can be used to compare different communities based on similarity or distance measures. Once communities have been clustered into groups, clone libraries can be prepared from sample(s) that are representative of each group in order to determine the phylogeny of the numerically abundant populations in a community. In this paper methods are introduced for the statistical analysis of T-RFLP data that include objective methods for (i) determining a baseline so that 'true' peaks in electropherograms can be identified; (ii) a means to compare electropherograms and bin fragments of similar size; (iii) clustering algorithms that can be used to identify communities that are similar to one another; and (iv) a means to select samples that are representative of a cluster that can be used to construct 16S rRNA gene clone libraries. The methods for data analysis were tested using simulated data with assumptions and parameters that corresponded to actual data. The simulation results demonstrated the usefulness of these methods in their ability to recover the true microbial community structure generated under the assumptions made. Software for implementing these methods is available at http://www.ibest.uidaho.edu/tools/trflp_stats/index.php.

Bacteria↗
PubMed2005

Haplotype diversity: the link between statistical and biological association.

In the rapidly growing field of association mapping in plants, the use of (marker) haplotypes rather than single markers can be an effective way of improving detection power. Here, we highlight the information that can be obtained from deducing the historical relationships between haplotypes. The ordering of haplotype classes according to deduced historical relationships should further enhance association detection power, but can also be used to predict the genotypic and phenotypic values of unobserved germplasm.

Genetic Markers↗
PubMed1986

Hemodynamics of in situ vein bypass: the role of side branch fistulae.

Ten patients undergoing femoral-popliteal and femoral-tibial in situ saphenous vein bypass for limb salvage were studied to determine the effects of side branch arteriovenous fistulae on flow through the distal end of the graft into the outflow artery. Studies were performed intraoperatively with electromagnetic flow probes. Following completion of proximal and distal anastomoses, flow was established through the graft and measured through its proximal and distal ends. Side branches were then ligated, and flow through the distal end of the graft measured again. Papaverine was administered and flow measured once more. Measured flows were consistent with those observed in previous studies, as were changes in flow induced by papaverine. Results indicate statistically significant diversion of blood through the fistulae, and a statistically significant increase in distal graft flow accompanying ligation of side branch fistulae. These data support the practice of routine side branch ligation during in situ bypass grafting.

Arteriovenous Fistula↗