Fitting mixture models to birth weight data: a case study.

Birth weights by gestational age are compared in two birth cohorts from Northern Finland, the first from 1966 and the second from 1985-1986. A curious fact in the data is that mean birth weight before the 39th week was lower in the latter series although the mean birth weight for the total series was higher. Similar findings have been reported in other series. A mixture model with the nonparametric regression function is proposed for studying the hypothesis that the difference was caused by more frequent gross errors in gestational assessment in the earlier cohort. The probability of an error in gestational assessment then greatly depends on the observed gestational age, which makes the mixture model nonstandard. Maximum likelihood solutions to the parameters in the proposed model were computed employing the general expectation-maximization (EM) algorithm. A technique for studying the effect of errors on the intrauterine weight gain curve is proposed and applied to our two birth cohorts. The risk of underestimation of gestational age seems to be larger in the previous series and the differences between the growth curves almost totally vanish when "corrected" by means of the mixture model.     

PeptideAtlas: a resource for target selection for emerging targeted proteomics workflows

A crucial part of a successful systems biology experiment is an assay that provides reliable, quantitative measurements for each of the components in the system being studied. For proteomics to be a key part of such studies, it must deliver accurate quantification of all the components in the system for each tested perturbation without any gaps in the data. This will require a new approach to proteomics that is based on emerging targeted quantitative mass spectrometry techniques. The PeptideAtlas Project comprises a growing, publicly accessible database of peptides identified in many tandem mass spectrometry proteomics studies and software tools that allow the building of PeptideAtlas, as well as its use by the research community. Here, we describe the PeptideAtlas Project, its contents and components, and show how together they provide a unique platform to select and validate mass spectrometry targets, thereby allowing the next revolution in proteomics.     

Strong-association-rule mining for large-scale gene-expression data analysis: a case study on human SAGE data

Background  

The association-rules discovery (ARD) technique has yet to be applied to gene-expression data analysis. Even in the absence of previous biological knowledge, it should identify sets of genes whose expression is correlated. The first association-rule miners appeared six years ago and proved efficient at dealing with sparse and weakly correlated data. A huge international research effort has led to new algorithms for tackling difficult contexts and these are particularly suited to analysis of large gene-expression matrices. To validate the ARD technique we have applied it to freely available human serial analysis of gene expression (SAGE) data.     

Evolution of invertebrate nervous systems: the Chaetognatha as a case study

Harzsch, S. and Wanninger, A. 2010. Evolution of invertebrate nervous systems: the Chaetognatha as a case study. —Acta Zoologica (Stockholm) 91 : 35–43 Although recent molecular studies indicate that Chaetognatha may be one of the earliest Bilaterian offshoots, the phylogenetic position of this taxon still is a matter of ongoing debate. In this contribution, we review recent attempts to contribute phylogenetic information on the Chaetognatha by analysing structure and development of their nervous system (neurophylogeny). Analysing this group of organisms also has a major impact on our understanding of nervous system evolution in Bilateria. We review recent evidence from this field and suggest that Urbilateria already was equipped with the genetic toolkit required to build a complex, concentrated central nervous system (CNS), although this was not expressed phenotypically so that Urbilateria was equipped with a nerve plexus and not a CNS. This implies that in the deep metazoan nodes, concentration of the ancestral plexus occurred twice independently, namely once after the protostome–deuterostome split on the branch leading to the protostomes (resulting in a ventrally positioned nerve cord) and once along the chordate line (with a dorsal nerve cord).     

Measuring genome divergence in bacteria: a case study using chlamydian data

We have studied the relative contribution of inversions, transpositions, deletions, and nucleotide substitutions to the evolution of Chlamydia trachomatis and Chlamydia pneumoniae. The minimal number of rearrangement events required for converting the gene order structure of one genome into that of the other was estimated to 59 +/- 6 events, including 13% inversions, 38% short inversions, and 49% transpositions. In contrast to previous findings, no examples of horizontal gene transfer subsequent to species divergence were identified, nor any evidence for an excessive number of tandem gene duplications. A statistical model was used to compare nucleotide frequencies for a set of genes uniquely present in one species to a set of orthologous genes present in both species. The two data sets were not significantly different, which is indicative of a low frequency of horizontal gene transfer events. This is based on the assumption that a foreign gene of different nucleotide content will not have become completely ameliorated, as verified by simulations of the amelioration rate at twofold and fourfold degenerate codon sites. The frequencies of nucleotide substitutions at twofold and fourfold degenerate sites, deletions, inversions, and translocations were estimated to 1.42, 0.62, 0.18, 0.01, and 0.01 per site, respectively.     

Fitting numerical solutions of differential equations to experimental data: a case study and some general remarks

A simple and efficient algorithm for least-squares estimation of the parameters of a numerically solved diffusion model is presented. The algorithm has been specially developed for the analysis of data obtained by vitreous fluorophotometry (a method in clinical eye research), but it has several straightforward generalizations which are also outlined in the paper.     

Incorporating expression data in metabolic modeling: a case study of lactate dehydrogenase

Integrating biological information from different sources to understand cellular processes is an important problem in systems biology. We use data from mRNA expression arrays and chemical kinetics to formulate a metabolic model relevant to K562 erythroleukemia cells. MAP kinase pathway activation alters the expression of metabolic enzymes in K562 cells. Our array data show changes in expression of lactate dehydrogenase (LDH) isoforms after treatment with phorbol 12-myristate 13-acetate (PMA), which activates MAP kinase signaling. We model the change in lactate production which occurs when the MAP kinase pathway is activated, using a non-equilibrium, chemical-kinetic model of homolactic fermentation. In particular, we examine the role of LDH isoforms, which catalyse the conversion of pyruvate to lactate. Changes in the isoform ratio are not the primary determinant of the production of lactate. Rather, the total concentration of LDH controls the lactate concentration.     

Classifying noisy protein sequence data: a case study of immunoglobulin light chains

SUMMARY: The classification of protein sequences obtained from patients with various immunoglobulin-related conformational diseases may provide insight into structural correlates of pathogenicity. However, clinical data are very sparse and, in the case of antibody-related proteins, the collected sequences have large variability with only a small subset of variations relevant to the protein pathogenicity (function). On this basis, these sequences represent a model system for development of strategies to recognize the small subset of function-determining variations among the much larger number of primary structure diversifications introduced during evolution. Under such conditions, most protein classification algorithms have limited accuracy. To address this problem, we propose a support vector machine (SVM)-based classifier that combines sequence and 3D structural averaging information. Each amino acid in the sequence is represented by a set of six physicochemical properties: hydrophobicity, hydrophilicity, volume, surface area, bulkiness and refractivity. Each position in the sequence is described by the properties of the amino acid at that position and the properties of its neighbors in 3D space or in the sequence. A structure template is selected to determine neighbors in 3D space and a window size is used to determine the neighbors in the sequence. The test data consist of 209 proteins of human antibody immunoglobulin light chains, each represented by aligned sequences of 120 amino acids. The methodology is applied to the classification of protein sequences collected from patients with and without amyloidosis, and indicates that the proposed modified classifiers are more robust to sequence variability than standard SVM classifiers, improving classification error between 5 and 25% and sensitivity between 9 and 17%. The classification results might also suggest possible mechanisms for the propensity of immunoglobulin light chains to amyloid formation.     

The interactions of neuropeptides with membrane model systems: a case study.

The interactions between the positively charged neuropeptides substance P (SP), bradykinin (BK), and zwitterionic Met-enkephalin (ME) neuropeptides, and negatively charged SDS and zwitterionic lysophosphatidylcholine (LPC) membrane model systems, have been investigated using one- and two-dimensional nmr experiments. Proton longitudinal relaxation studies were used to characterize these interactions as intrinsic or extrinsic. An extrinsic interaction are similar to those observed for extrinsic membrane proteins. An intrinsic interaction are similar to those observed for intrinsic membrane proteins, and would require that the hydrophobic residues penetrate or insert into the hydrophobic core of the membrane. The interactions between both SP and BK and SDS, based on nmr results, may be characterized as intrinsic, and the interaction between ME and SDS may be characterized as extrinsic. Two-dimensional nuclear Overhauser enhancement spectroscopy experiments proved the insertion of the phenylalanine residues on both SP and BK into the hydrophobic core of SDS micelles. The interaction between SP and BK with LPC based on nmr results are characterized as extrinsic, with the interaction between ME and SDS characterized as weakly intrinsic.     

Proximate personhood as a standard for making difficult treatment decisions: imperiled newborns as a case study

... The standard of personhood is gaining increased attention and prominence. The essential claim is that only individuals with capacities for significant cerebral functioning possess a morally unique claim to existence. Persons are defined as individuals who are self-aware and capable of self-direction (Engelhardt), able to enter meaningful relationships (McCormick), capable of minimal independent existence (Shelp), and in possession of a minimal 20-40 I.Q. (Joseph Fletcher). These are "high standard" personhood positions (those holding higher-brain related criteria). It is a commonplace with most such positions that newborns -- all newborns -- are not, strictly speaking, persons. That is, newborns are not self-aware, intentionally choosing individuals.... The thesis of this essay is that a developing individual's right to life increases as he or she approaches the threshold of personal life. That is, the more a newborn approximates -- or is proximate to -- undisputed personhood (e.g. the status of readers of this essay), the greater his or her claim to life. The two pivotal criteria for determining personhood are the potentiality for and development toward becoming an undisputed personal being. I am presupposing, for purposes of argument, that the handicapped infant would not be an excessive familial burden or an inordinate financial load for society, one an ancient and the other a modern criterion. That condition granted, this essay contends that if an imperiled newborn is reasonably projected to reach at least minimal personal capacity, treatment should be given.     

Introduction to flow cytometry data file standard

The Data File Standards Committee of the Society for Analytical Cytology presents a Standard to be used for the storage of data associated with flow cytometric measurements. The Standard specifies a format that provides for the inclusion of all information necessary to fully describe: 1) the instrument used for the measurement; 2) the sample measured; 3) the data obtained; and 4) the results of analysis of the data. The Committee and the Society for Analytical Cytology point out that the use of this Standard by all those individuals and companies that generate or use data taken with flow cytometers or generate methods of analysis for the data will encourage the sharing of such data and methods of analysis.