bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistical interpretation of machine learning-based feature importance scores for biomarker discovery
Authors: Huynh-Thu Vân Anh , Saeys Yvan , Wehenkel Louis , Geurts Pierre 
Published: April 2012

AbstractMotivation: Univariate statistical tests are widely used for biomarker discovery in bioinformatics. These procedures are simple, fast and their output is easily interpretable by biologists but they can only identify variables that provide a significant amount of information in isolation from the other variables. As biological processes are expected to involve complex interactions between variables, univariate methods thus potentially miss some informative biomarkers. Variable relevance scores provided by machine learning techniques, however, are potentially able to highlight multivariate interacting effects, but unlike the p-values returned by univariate tests, these relevance scores are usually not statistically interpretable. This lack of interpretability hampers the determination of a relevance threshold for extracting a feature subset from the rankings and also prevents the wide adoption of these methods by practicians.Results: We evaluated several, existing and novel, procedures that extract relevant features from rankings derived from machine learning approaches. These procedures replace the relevance scores with measures that can be interpreted in a statistical way, such as p-values, false discovery rates, or family wise error rates, for which it is easier to determine a significance level. Experiments were performed on several artificial problems as well as on real microarray datasets. Although the methods differ in terms of computing times and the tradeoff, they achieve in terms of false positives and false negatives, some of them greatly help in the extraction of truly relevant biomarkers and should thus be of great practical interest for biologists and physicians. As a side conclusion, our experiments also clearly highlight that using model performance as a criterion for feature selection is often counter-productive.Availability and implementation: Python source codes of all tested methods, as well as the MATLAB scripts used for data simulation, can be found in the Supplementary Material.Contact: vahuynh@ulg.ac.be, or p.geurts@ulg.ac.beSupplementary information: Supplementary data are available at Bioinformatics online.
CNVRuler: a copy number variation-based case–control association analysis tool
Authors: Kim Ji-Hong , Hu Hae-Jin , Yim Seon-Hee , Bae Joon Seol , Kim Seon-Young , Chung Yeun-Jun 
Published: April 2012

Abstract
Summary: The method for genome-wide association study (GWAS) based on copy number variation (CNV) is not as well established as that for single nucleotide polymorphism (SNP)–GWAS. Although there are several tools for CNV association studies, most of them do not provide appropriate definitions of CNV regions (CNVRs), which are essential for CNV-association studies. Here we present a user-friendly program called CNVRuler for CNV-association studies. Outputs from the 10 most common CNV defining algorithms can be directly used as input files for determining the three different definitions of CNVRs. Once CNVRs are defined, CNVRuler supports four kinds of statistical association tests and options for population stratification. CNVRuler is based on the open-source programs R and Java from Sun Microsystems.
Availability: CNVRuler software is available with an online manual at the website, www.ircgp.com/CNVRuler/index.html
Contact: yejun@catholic.ac.kr.
Supplementary information: Supplementary data are available at Bioinformatics online.
Improving the TFold test for differential shotgun proteomics
Authors: Carvalho Paulo C. , Yates John R. , Barbosa Valmir C. 
Published: April 2012

AbstractSummary: We present an updated version of the TFold software for pinpointing differentially expressed proteins in shotgun proteomics experiments. Given an FDR bound, the updated approach uses a theoretical FDR estimator to maximize the number of identifications that satisfy both a fold-change cutoff that varies with the t-test P-value as a power law and a stringency criterion that aims to detect lowly abundant proteins. The new version has yielded significant improvements in sensitivity over the previous one.Availability: Freely available for academic use at http://pcarvalho.com/patternlab.Contact: paulo@pcarvalho.com
DecoyFinder: an easy-to-use python GUI application for building target-specific decoy sets
Authors: Cereto-Massagué Adrià , Guasch Laura , Valls Cristina , Mulero Miquel , Pujadas Gerard , Garcia-Vallvé Santiago 
Published: April 2012

Abstract
Summary: Decoys are molecules that are presumed to be inactive against a target (i.e. will not likely bind to the target) and are used to validate the performance of molecular docking or a virtual screening workflow. The Directory of Useful Decoys database (http://dud.docking.org/) provides a free directory of decoys for use in virtual screening, though it only contains a limited set of decoys for 40 targets.To overcome this limitation, we have developed an application called DecoyFinder that selects, for a given collection of active ligands of a target, a set of decoys from a database of compounds. Decoys are selected if they are similar to active ligands according to five physical descriptors (molecular weight, number of rotational bonds, total hydrogen bond donors, total hydrogen bond acceptors and the octanol–water partition coefficient) without being chemically similar to any of the active ligands used as an input (according to the Tanimoto coefficient between MACCS fingerprints). To the best of our knowledge, DecoyFinder is the first application designed to build target-specific decoy sets.
Availability: A complete description of the software is included on the application home page. A validation of DecoyFinder on 10 DUD targets is provided as Supplementary Table S1. DecoyFinder is freely available at http://URVnutrigenomica-CTNS.github.com/DecoyFinder
Contact: santi.garcia-vallve@urv.cat
Supplementary information: Supplementary data are available at Bioinformatics online.
Semantic integration of physiology phenotypes with an application to the Cellular Phenotype Ontology
Authors: Hoehndorf Robert , Harris Midori A. , Herre Heinrich , Rustici Gabriella , Gkoutos Georgios V. 
Published: April 2012

Abstract
Motivation: The systematic observation of phenotypes has become a crucial tool of functional genomics, and several large international projects are currently underway to identify and characterize the phenotypes that are associated with genotypes in several species. To integrate phenotype descriptions within and across species, phenotype ontologies have been developed. Applying ontologies to unify phenotype descriptions in the domain of physiology has been a particular challenge due to the high complexity of the underlying domain.
Results: In this study, we present the outline of a theory and its implementation for an ontology of physiology-related phenotypes. We provide a formal description of process attributes and relate them to the attributes of their temporal parts and participants. We apply our theory to create the Cellular Phenotype Ontology (CPO). The CPO is an ontology of morphological and physiological phenotypic characteristics of cells, cell components and cellular processes. Its prime application is to provide terms and uniform definition patterns for the annotation of cellular phenotypes. The CPO can be used for the annotation of observed abnormalities in domains, such as systems microscopy, in which cellular abnormalities are observed and for which no phenotype ontology has been created.
Availability and implementation: The CPO and the source code we generated to create the CPO are freely available on http://cell-phenotype.googlecode.com.
Contact: rh497@cam.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
Conversion of viable but nonculturable enteric bacteria  to culturable by co‐culture with eukaryotic cells
Authors: Senoh Mitsutoshi , Ghosh‐Banerjee Jayeeta , Ramamurthy Thandavarayan , Colwell Rita R. , Miyoshi Shin‐ichi , Nair G. Balakrish , Takeda Yoshifumi 
Published: April 2012

ABSTRACT Viable but nonculturable (VBNC) Vibrio cholerae non‐O1/non‐O139, V. parahaemolyticus, enterohemorrhagic Escherichia coli, enterotoxigenic E. coli, enteropathogenic E. coli, Shigella flexneri, and Salmonella enterica were converted to the culturable state by co‐culture with selected eukaryotic cells, e.g., HT‐29, Caco‐2, T84, HeLa, Intestine 407, and CHO cells.
Phenotypic characterization of Aspergillus niger and Candida albicans grown under simulated microgravity using a three‐dimensional clinostat
Authors: Yamazaki Takashi , Yoshimoto Maki , Nishiyama Yayoi , Okubo Yoichiro , Makimura Koichi 
Published: April 2012

ABSTRACTThe living and working environments of spacecraft become progressively contaminated by a number of microorganisms. A large number of microorganisms, including pathogenic microorganisms, some of which are fungi, have been found in the cabins of space stations. However, it is not known how the characteristics of microorganisms change in the space environment. To predict how a microgravity environment might affect fungi, and thus how their characteristics could change on board spacecraft, strains of the pathogenic fungi Aspergillus niger and Candida albicans were subjected to on‐ground tests in a simulated microgravity environment produced by a three‐dimensional (3D) clinostat. These fungi were incubated and cultured in a 3D clinostat in a simulated microgravity environment. No positive or negative differences in morphology, asexual reproductive capability, or susceptibility to antifungal agents were observed in cultures grown under simulated microgravity compared to those grown in normal earth gravity (1 G). These results strongly suggest that a microgravity environment, such as that on board spacecraft, allows growth of potentially pathogenic fungi that can contaminate the living environment for astronauts in spacecraft in the same way as they contaminate residential areas on earth. They also suggest that these organisms pose a similar risk of opportunistic infections or allergies in astronauts as they do in people with compromised immunity on the ground and that treatment of fungal infections in space could be the same as on earth.
Immunohistochemical Ki67 labeling index has similar proliferation predictive power to various gene signatures in breast cancer
Authors: Niikura Naoki , Iwamoto Takayuki , Masuda Shinobu , Kumaki Nobue , Xiaoyan Tang , Shirane Masatoshi , Mori Kazushige , Tsuda Banri , Okamura Takuho , Saito Yuki , Suzuki Yasuhiro , Tokuda Yutaka 
Published: April 2012

The objective of this study was to examine the association between the immunohistochemical Ki67 labeling index (IHC Ki67), Ki67 mRNA expression level, and first‐generation gene signatures in a cohort of breast cancer patients. We assessed associations between IHC Ki67 and first‐generation gene signatures in a panel of 39 tumor samples, using an oligonucleotide microarray. Gene expression analyses included Ki67 alone (MKi67), 21‐gene signature, mitosis kinome score signature, and genomic grade index. Correlation coefficients were calculated by Spearman's rank correlation test. In all cases, IHC Ki67, MKi67, and three genetic markers were highly correlated (ρ, 0.71–0.97). Estrogen receptor (ER)‐positive cases showed strong correlations between IHC Ki67 and other signatures (ρ, 0.79–0.83). The ER‐negative cases showed slightly lower correlations (ρ, 0.58–0.73). In ER‐positive cases, the low IHC Ki67 group showed significantly longer relapse‐free survival than the high IHC Ki67 group (P = 0.007). This difference was confirmed by multivariate analysis. Our data indicate that IHC Ki67 shows similar predictive power for proliferation in ER‐positive cancers as genomic markers. Further study of IHC Ki67 is needed to define prognostic factors and predictive factors for chemotherapy using central laboratory assessment. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02319.x, 2012)
The impact of MMX mesalazine on disease‐specific health‐related quality of life in ulcerative colitis patients
Authors: Solomon D. , Yarlas A. , Hodgkins P. , Karlstadt R. , Yen L. , Kane S. 
Published: April 2012

SummaryBackgroundPast studies with ulcerative colitis (UC) patients indicate that disease activity strongly predicts health‐related quality of life (HRQL).AimTo examine the degree to which daily treatment with MMX mesalazine predicts improved HRQL for patients with active UC and with stable HRQL for patients with quiescent UC.MethodsData from two phases of a multicentre open‐label trial were examined. In the acute phase, 132 patients with mild‐to‐moderate active UC received MMX mesalazine 2.4–4.8 g/day for 8 weeks, while 206 patients with quiescent UC received MMX mesalazine 2.4 g/day for a 12‐month maintenance phase. Disease‐specific HRQL was measured at baseline and endpoint of each phase using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Repeated‐measures anova models examined baseline‐endpoint changes in SIBDQ, stool frequency (SF), and rectal bleeding severity (RBS). Correlations assessed the associations between SIBDQ and SF/RBS scores, while ancova techniques tested the sensitivity of SIBDQ to disease recurrence.ResultsSIBDQ scores significantly increased for active mild‐to‐moderate UC patients following 8 weeks of treatment, while SIBDQ scores remained stable for quiescent UC patients following 12 months of treatment. Changes in SIBDQ scores correlated significantly with changes in SF and RBS scores. Patients with recurrent UC at maintenance phase endpoint had significantly lower SIBDQ scores than nonrecurrent patients.ConclusionsDaily MMX mesalazine therapy was associated with significant improvement in disease‐specific HRQL for patients with mild‐to‐moderate active UC and with the maintenance of HRQL for patients with quiescent UC. In both patient groups, HRQL was significantly associated with disease activity.
Identification and management of poor response to growth‐promoting therapy in children with short stature
Authors: Bang Peter , Ahmed S. Faisal , Argente Jesús , Backeljauw Philippe , Bettendorf Markus , Bona Gianni , Coutant Régis , Rosenfeld Ron G. , Walenkamp Marie‐José , Savage Martin O. 
Published: April 2012

SummaryGrowth hormone (GH) is widely prescribed for children with short stature across a range of growth disorders. Recombinant human (rh) insulin‐like growth factor‐1 (rhIGF‐1) therapy is approved for severe primary IGF‐I deficiency – a state of severe GH resistance. Evidence is increasing for an unacceptably high rate of poor or unsatisfactory response to growth‐promoting therapy (i.e. not leading to significant catch up growth) in terms of change in height standard deviation score (SDS) and height velocity (HV) in many approved indications. Consequently, there is a need to define poor response and to prevent or correct it by optimizing treatment regimens within accepted guidelines. Recognition of a poor response is an indication for action by the treating physician, either to modify the therapy or to review the primary diagnosis leading either to discontinuation or change of therapy. This review discusses the optimal investigation of the child who is a candidate for GH or IGF‐1 therapy so that a diagnosis‐based choice of therapy and dosage can be made. The relevant parameters in the evaluation of growth response are described together with the definitions of poor response. Prevention of poor response is addressed by discussion of strategy for first‐year management with GH and IGF‐1. Adherence to therapy is reviewed as is the recommended action following the identification of the poorly responding patient. The awareness, recognition and management of poor response to growth‐promoting therapy will lead to better patient care, greater cost‐effectiveness and increased opportunities for clinical benefit.
Yield, quality and ensilage characteristics of whole‐crop maize and of the cob and stover components: harvest date and hybrid effects
Authors: Lynch J. P. , O’Kiely P. , Doyle E. M. 
Published: April 2012

AbstractThe objective of the study was to determine the effects of maize hybrid and harvest date on the yield, quality and subsequent conservation characteristics of whole‐crop, cob and stover silages. The experiment had a split‐plot design, with three main plots (date of harvest) and six subplots (hybrid) in each of three replicate blocks. Four maize hybrids (Tassilo, Beethoven, Andante and Nescio) were conventional hybrids used in commercial livestock production in Ireland, and two were categorized as high‐biomass hybrids (Atletico and KXA 7211). The three harvest dates – 16 September, 7 October and 28 October – represented early, normal and late harvests respectively. Averaged across hybrids, harvesting on 16 September reduced the DM yield (P < 0·05) and starch concentration (P < 0·01) of whole‐crop and cob, and decreased the neutral detergent fibre (P < 0·05) and acid detergent fibre (P < 0·01) contents of stover. Later harvesting date generally resulted in a more restricted, heterolactic fermentation that was associated with increased dry‐matter (DM) content at ensiling. Whole‐crop and stover from Atletico and KXA 7211 generally had higher DM yields (P < 0·05) and a more extensive fermentation compared to Tassilo, Andante and Nescio. Despite the high‐biomass hybrids having a higher DM yield than conventional hybrids, the high‐biomass hybrids had a lower (P < 0·05) content of cob and a corresponding higher (P < 0·05) content of stover. The changes in proportions of cob and stover in whole‐crop maize with later harvesting significantly influenced its silage digestibility and conservation characteristics.
Evaluating population recovery for sea turtles under nesting beach protection while accounting for nesting behaviours and changes in availability
Authors: Thorson James T. , Punt André E. , Nel Ronel 
Published: April 2012

Summary1. Sea turtles and sea birds generally have high conservation importance world‐wide and are often difficult to survey except when present on nesting grounds. Consequently, many such surveys tag nesting individuals and use tag‐resighting models to estimate population size and assess anthropogenic impacts. However, the conventional Cormac–Jolly–Seber (CJS) tag‐resighting model is problematic for these species for three reasons: individuals often return to nesting areas in alternating years because of high energetic costs for nesting, estimated detectability confounds changes in survey efficiency with availability on the surveyed beach, and tag loss is confounded with mortality.2. We develop a robust design model that uses higher‐order Markovian transitions to approximate skip‐nesting behaviours and incorporates multiple observations for each nesting individual to estimate changes in availability (the probability of returning to the surveyed area rather than alternative nesting areas). We approximate time‐varying effects using a flexible spline method and demonstrate the model using data for leatherback sea turtles Dermochelys coriacea and loggerhead sea turtles Caretta caretta in South Africa.3. The apparent lack of recovery for leatherback sea turtles after implementing beach protection, as observed in nest count data, is likely to be due to declining detectability caused by decreased availability during population recovery (e.g. habitat expansion). By contrast, loggerhead sea turtles have approximately constant detectability and stable abundance since the 1970s.4. We find that increased fishing effort has no explanatory power regarding changes in survival for either species.5. Synthesis and applications. Based on study results, we recommend that future tag‐resighting programmes for sea turtles and birds are accompanied periodically by count surveys beyond the regularly monitored nesting areas to evaluate evidence of range expansion. However, the identification of range expansion in historical data is only possible using model‐based inference and robust design methods such as presented in this study.
Impact of Pleistocene aridity oscillations on the population history of a widespread, vagile Australian mammal, Macropus fuliginosus
Authors: Neaves Linda E. , Zenger Kyall R. , Prince Robert I. T. , Eldridge Mark D. B. 
Published: April 2012

AbstractAim  Climatic fluctuations during the Pleistocene have shaped the population structure of many extant taxa. However, few studies have examined widespread species inhabiting the Australian continent, where periods of increased aridity characterized the Pleistocene. Here we investigate the phylogeography and population history of a widespread and vagile southern Australian marsupial, the western grey kangaroo (Macropus fuliginosus).Location  Southern Australia.Methods  We examined the variation of the mitochondrial DNA (mtDNA) control region from 511 individuals of M. fuliginosus sampled throughout their transcontinental distribution. Maximum likelihood and Bayesian analyses were used to investigate the phylogeography and coalescence analyses were then used to test hypothesized biogeographical scenarios.Results  The combined results of the phylogeographical and coalescence analyses revealed a complex evolutionary history. Macropus fuliginosus originated in the south‐west of the continent, with north‐western and south‐western populations subsequently diverging as a result of vicariance events during the mid‐Pleistocene. Subsequent arid phases affected these populations differently. In the north‐west, the expansion and contraction of the arid zone resulted in repeated vicariance events and multiple divergent north‐western mtDNA subclades. In contrast, the south‐western population was less impacted by climatic oscillations but gave rise to a major transcontinental eastward expansion.Main conclusions  Macropus fuliginosus exhibits the genetic signature of divergence due to unidentified barriers in south‐western Western Australia, while previously identified barriers across southern Australia appear to have had little impact despite evidence of a broad‐scale range expansion prior to the Last Glacial Maximum (LGM). This pattern of localized expansion and contraction is comparable to unglaciated regions in both the Northern and Southern Hemispheres. Furthermore, this study indicates that despite the potential similarities between Northern Hemisphere glaciation and the activation of dune systems in the Australian arid zone, both of which rendered large areas inhospitable, the biotic responses and resultant phylogeographical signatures are dissimilar. Whereas a limited number of major geographically concordant refugia are observed in glaciated areas, the Southern Hemisphere arid zone appears to be associated with multiple species‐specific idiosyncratic refugia.