8233582
Statistical agglomeration: peak summarization for direct infusion lipidomics
MOTIVATION
Quantification of lipids is a primary goal in lipidomics. In direct infusion/injection (or shotgun) lipidomics, accurate downstream identification and quantitation requires accurate summarization of repetitive peak measurements. Imprecise peak summarization multiplies downstream error by propagating into species identification and intensity estimation. To our knowledge, this is the first analysis of direct infusion peak summarization in the literature.


RESULTS
We present two novel peak summarization algorithms for direct infusion samples and compare them with an off-machine ad hoc summarization algorithm as well as with the propriety Xcalibur algorithm. Our statistical agglomeration algorithm reduces peakwise error by 38% mass/charge (m/z) and 44% (intensity) compared with the ad hoc method over three datasets. Pointwise error is reduced by 23% (m/z). Compared with Xcalibur, our statistical agglomeration algorithm produces 68% less m/z error and 51% less intensity error on average on two comparable datasets.


AVAILABILITY
The source code for Statistical Agglomeration and the datasets used are freely available for non-commercial purposes at https://github.com/optimusmoose/statistical_agglomeration. Modified Bin Aggolmeration is freely available in MSpire, an open source mass spectrometry package at https://github.com/princelab/mspire/.
27343241
Novel algorithms and the benefits of comparative validation
Contact: 2robsmith@gmail.com, jtprince@chem.byu.edu Bioinformatic research has produced a large volume of proposed algorithmic solutions to a host of problems. Whether presented as a processing step in a clinical experiment or treated in a stand-alone publication, novel bioinformatic algorithms are often not subjected to the thorough comparative evaluation endured by their counterparts in other closely related fields—such as computer science—where an algorithm unevaluated against extant methods is considered unpublishable. Two audiences are interested in algorithmic publications: the practitioner, who may use the algorithm, and the researcher, who will work to develop solutions superior to those extant. We argue that failure during the review/publication process to require comparative evaluation for novel algorithms is detrimental to both parties. To demonstrate the dilemma, we conducted a case study of novel LC-MS alignment algorithms. Of the 48 publications from 2001 to 2012 that present alignment algorithms of which we are aware, 60% include no comparison to other methods. Another 20%
6543991
Rubabel: wrapping open Babel with Ruby
BackgroundThe number and diversity of wrappers for chemoinformatic toolkits suggests the diverse needs of the chemoinformatic community. While existing chemoinformatics libraries provide a broad range of utilities, many chemoinformaticians find compiled language libraries intimidating, time-consuming, arcane, and verbose. Although high-level language wrappers have been implemented, more can be done to leverage the intuitiveness of object-orientation, the paradigms of high-level languages, and the extensibility of languages such as Ruby. We introduce Rubabel, an intuitive, object-oriented suite of functionality that substantially increases the accessibily of the tools in the Open Babel chemoinformatics library.ResultsRubabel requires fewer lines of code than any other actively developed wrapper, providing better object organization and navigation, and more intuitive object behavior than extant solutions. Moreover, Rubabel provides a convenient interface to the many extensions currently available in Ruby, greatly streamlining otherwise onerous tasks such as creating web applications that serve up Rubabel functionality.ConclusionsRubabel is powerful, intuitive, concise, freely available, cross-platform, and easy to install. We expect it to be a platform of choice for new users, Ruby users, and some users of current solutions.
15927414
LC-MS alignment in theory and practice: a comprehensive algorithmic review
Liquid chromatography-mass spectrometry is widely used for comparative replicate sample analysis in proteomics, lipidomics and metabolomics. Before statistical comparison, registration must be established to match corresponding analytes from run to run. Alignment, the most popular correspondence approach, consists of constructing a function that warps the content of runs to most closely match a given reference sample. To date, dozens of correspondence algorithms have been proposed, creating a daunting challenge for practitioners in algorithm selection. Yet, existing reviews have highlighted only a few approaches. In this review, we describe 50 correspondence algorithms to facilitate practical algorithm selection. We elucidate the motivation for correspondence and analyze the limitations of current approaches, which include prohibitive runtimes, numerous user parameters, model limitations and the need for reference samples. We suggest and describe a paradigm shift for overcoming current correspondence limitations by building on known liquid chromatography-mass spectrometry behavior.
2304899
Controlling for confounding variables in MS-omics protocol: why modularity matters
As the field of bioinformatics research continues to grow, more and more novel techniques are proposed to meet new challenges and improvements upon solutions to long-standing problems. These include data processing techniques and wet lab protocol techniques. Although the literature is consistently thorough in experimental detail and variable-controlling rigor for wet lab protocol techniques, bioinformatics techniques tend to be less described and less controlled. As the validation or rejection of hypotheses rests on the experiment's ability to isolate and measure a variable of interest, we urge the importance of reducing confounding variables in bioinformatics techniques during mass spectrometry experimentation.
19926226
Sensitivity to scale in contingent valuation: the importance of the budget constraint.
The possible insensitivity of willingness-to-pay (WTP) values to changes in scale continues to cause concern within the contingent valuation (CV) literature. Although several reasons for this phenomenon have been suggested, empirical evidence both supports and refutes insensitivity. This paper presents data that suggest that insensitivity may be significantly determined by the individual's budget constraint: the higher the proportion of income the expressed WTP represents, the greater the insensitivity of that WTP to changes in the scale of the good, irrespective of changes in underlying marginal utility. The methodological implication for CV studies in health care is outlined.
33043353
Can we estimate the 'social' value of a QALY? Four core issues to resolve.
There is growing interest in estimating the 'societal' willingness to pay (WTP) for a quality adjusted life year (QALY) to help public health system decision-makers determine whether a health care programme should/not be undertaken. However, there is a lack of clarity in this debate concerning four core issues: (i) is 'social' WTP simply the sum of 'individual' WTP; (ii) will 'individual' WTP map directly into 'social' WTP; (iii) is 'personal' income the appropriate budget constraint; (iv) should WTP be adjusted for ability to pay? This paper outlines the relevance and importance of each of these issues in the hope of encouraging a wider debate on the core issues that empirical studies will have to explore to discover whether such a value may be obtained.
1484363
Public health evaluation in the twenty-first century: time to see the wood as well as the trees.
This paper argues that concepts, methodologies and practices within public health need further development if they are to be sufficient to allow us to develop, undertake and evaluate interventions in the twenty-first century. The public health profession, and the disciplines that contribute to it, maintains the historical focus upon detailed micro analysis (individual and health sector) and not broader macro analysis (societal and system). This brief paper suggests why this is and outlines three challenges it poses: specifying and evaluating outcomes; specifying and understanding complex causal pathways in social interventions and the development of multisector evaluation, to meet information demands from multiple stakeholders. While there is general agreement that public health evaluation needs development, this paper argues that the focus needs to be more upon a broader evaluative space than is currently practiced. There is a need to move beyond primary and secondary health-related effects upon individuals, and focus more on evaluation of the wider range and distribution of direct and indirect effects upon individuals, communities and populations. That is, those involved in public health evaluation need to step back and first consider the wood before focusing in on specific trees.
3424059
Alterations in the hypothalamic pituitary adrenal axis during pregnancy and the placental clock that determines the length of parturition.
Although corticotrophin releasing hormone (CRH) was initially identified as a hypothalamic peptide it is also synthesised in the placenta and secreted into both the maternal and fetal circulation. The presence of large molecular weight forms in the placenta suggest that secretion may be constitutive rather that regulated. Placental CRH is bioactive but causes only modest increases in ACTH and cortisol in the pregnant woman because of agonist induced desensitisation of pituitary CRH receptors. CRH concentrations increase exponentially in maternal plasma as gestation advances. Elevated concentrations, compared with gestational age matched controls, occur in patients in preterm labour. The exponential curve describing the CRH increase is shifted to the left in women who will subsequently deliver preterm and to the right in women who will deliver post dates indicating that CRH is linked to a placental clock which determines the length of gestation. Maternal plasma CRH concentrations may be useful in identifying women at high risk of preterm delivery and CRH antagonists may prevent preterm labour. As significant CRH production by the placenta is restricted to primates future research must take into account the species specificity of the mechanisms regulating parturition.
33674054
Timing of perinatal human immunodeficiency virus type 1 infection and rate of neurodevelopment. The Women and Infant Transmission Study Group.
BACKGROUND
Identifying HIV-1-infected children who are at greatest risk for disease-related morbidities is critical for optimal therapeutic as well as preventive care. Several factors have been implicated in HIV-1 disease onset and severity, including maternal and infant host characteristics, viral phenotype and timing of HIV-1 infection. Early HIV-1 culture positivity, i.e. intrauterine infection, has been associated with poor immunologic, virologic and clinical outcomes in children of HIV-infected women. However, a direct effect of timing of infection on neurodevelopmental outcome in infancy has not yet been identified.


METHODS
Serial neurodevelopmental assessments were performed with 114 infants vertically infected with HIV-1 in a multicenter natural history, longitudinal study. Median mental and motor scores were compared at three time points. Longitudinal regression analyses were used to evaluate the neurodevelopmental functioning of children with early positive cultures and those with late positive cultures.


RESULTS
Early infected infants scored significantly lower than late infected infants by 24 months of age and beyond on both mental (P = 0.05) and motor (P = 0.03) measures. Early HIV-1 infection was associated with a decline in estimated motor scores of 1 standard score point per month compared with 0.28 point in the late infected group (P < 0.02). Estimated mental scores of the early infected group declined 0.72 point/ month, whereas the average decline of the late infected group was 0.30 point/month (P < 0.13).


CONCLUSION
Early HIV-1 infection increases a child's risk for poor neurodevelopmental functioning within the first 30 months of life.