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EDISON-WMW: Exact Dynamic Programing Solution of the Wilcoxon–Mann–Whitney Test

Genomics, Proteomics & Bioinformatics 2016年第1期14卷 55-61页

作者： Alexander Marx Christina Backes Eckart Meese hans-peter lenhof Andreas Keller Chair for Clinical Bioinformatics Medical Faculty Saarland University Department of Human Genetics Saarland University University Hospital Chair for Bioinformatics Saarland University

In many research disciplines, hypothesis tests are applied to evaluate whether findings are statistically significant or could be explained by chance. The Wilcoxon-Mann-Whitney （WMW） test is among the most popular hypothesis tests in medicine and life science to analyze if two groups of samples are equally distributed. This nonparametric statistical homogeneity test is commonly applied in molecular diagnosis. Generally, the solution of the WMW test takes a high combinatorial effort for large sample cohorts containing a significant number of ties. Hence, P value is frequently approximated by a normal distribution. We developed EDISON-WMW, a new approach to calcu- late the exact permutation of the two-tailed unpaired WMW test without any corrections required and allowing for ties. The method relies on dynamic programing to solve the combinatorial problem of the WMW test efficiently. Beyond a straightforward implementation of the algorithm, we pre- sented different optimization strategies and developed a parallel solution. Using our program, the exact P value for large cohorts containing more than 1000 samples with ties can be calculated within minutes. We demonstrate the performance of this novel approach on randomly-generated data, benchmark it against 13 other commonly-applied approaches and moreover evaluate molec- ular biomarkers for lung carcinoma and chronic obstructive pulmonary disease （COPD）. We foundthat approximated P values were generally higher than the exact solution provided by EDISON- WMW. Importantly, the algorithm can also be applied to high-throughput omics datasets, where hundreds or thousands of features are included. To provide easy access to the multi-threaded version of EDISON-WMW, a web-based solution of our algorithm is freely available at http：// ***/software/wtest/.

关键词： Wilcoxon-Mann-Whitneytest:Wilcoxon rank-sum test Dynamic programing Exact permutation Parallel optimization

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Genome-wide MicroRNA Expression Profiles in COPD: Early Predictors for Cancer Development

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Genomics, Proteomics & Bioinformatics 2018年第3期16卷 162-171页

作者： Andreas Keller Tobias Fehlmann Nicole Ludwig Mustafa Kahraman Thomas Laufer Christina Backes Claus Vogelmeier Caroline Diener Frank Biertz Christian Herr Rudolf A. Jorres hans-peter lenhof Eckart Meese Robert Bals Clinical Bioinformatics Saarland University 66123 Saarbriieken Germany Department of Human Genetics Saarland University Hospital 66421 Homburg Germany Hummingbird Diagnostics GmbH 69120 Heidelberg Germany Department of Internal Medicine Division for Pulmonary Diseases Philipps University of Marburg 35043 Marburg Germany Institute for Biostatistics Hannover Medical School 30625 Hanover Germany Department of Internal Medicine V- Pulmonology AlIergology Intensive Care Medicine Saarland University Hospital 66421 Homburg Germany Institute and Outpatient Clinic for Occupational Social and Environmental Medicine Comprehensive Pneumology Center Munich (CPC-M) Ludwig-Maximilians-University Munich Member of the German Center for Lung Research ( DZL) 80539 Munich Germany Bioinformatics Saarland University 66123 Saarbrucken Germany Center for Bioinformatics Saarland University 66123 Saarbrucken Germany

Chronic obstructive pulmonary disease （COPD） significantly increases the risk of developing cancer. Biomarker studies frequently follow a case-control set-up in which patients diagnosed with a disease are compared to controls. Longitudinal cohort studies such as the COPD-centered German COPD and SYstemic consequences-COmorbidities NETwork （COSYCONET） study provide the patient and biomaterial base for discovering predictive molecular markers. We asked whether microRNA （miRNA） profiles in blood collected from COPD patients prior to a tumor diagnosis could support an early diagnosis of tumor development independent of the tumor type. From 2741 participants of COSYCONET diagnosed with COPD, we selected 534 individuals including 33 patients who developed cancer during the follow-up period of 54 months and 501 patients who did not develop cancer, but had similar age, gender and smoking history. Genome-wide miRNA profiles were generated and evaluated using machine learning techniques. For patients developing cancer we identified nine miRNAs with significantly decreased abundance （two-tailed unpaired t-test adjusted for multiple testing P 〈 0.05）, including members of the miR-320 family. The identified miRNAs regulate different cancer-related pathways including the MAPK pathway （P - 2.3 × 10 -5）. We also observed the impact of confounding factors on the generated miRNA profiles, underlining the value of our matched analysis. For selected miRNAs, qRT-PCR analysis was applied to validate the results. In conclusion, we identified several miRNAs in blood of COPD patients, which could serve as candidates for biomarkers to help identify COPD patients at risk of developing cancer.

关键词： microRNA Cancer COPD Lung Biomarker COSYCONET

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Machine Learning to Detect Alzheimer’s Disease from Circulating Non-coding RNAs

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Genomics, Proteomics & Bioinformatics 2019年第4期17卷 430-440页

作者： Nicole Ludwig Tobias Fehlmann Fabian Kern Manfred Gogol Walter Maetzler Stephanie Deutscher Simone Gurlit Claudia Schulte Anna-Katharina von Thaler Christian Deuschle Florian Metzger Daniela Berg Ulrike Suenkel Verena Keller Christina Backes hans-peter lenhof Eckart Meese Andreas Keller Department of Human Genetics Saarland University66421 Homburg/SaarGermany Chair for Clinical Bioinformatics Saarland University66123 Saarbru¨ckenGermany Institut fur Gerontologie Universitat Heidelberg69047 HeidelbergGermany Department of Neurology Christian-Albrechts-University of Kiel24118 KielGermany Center for Neurology and Hertie Institute for Clinical Brain Research Department of NeurodegenerationUniversity of Tuebingen72074 TuebingenGermany German Center for Neurodegenerative Diseases(DZNE) 72076 TuebingenGermany Department of Anesthesiology and Intensive Care St.Franziskus Hospital Muenster48145 MuensterGermany Department of Psychiatry and Psychotherapy University Hospital Tuebingen72016 TuebingenGermany Department of Medicine II Saarland University Medical Center66421 Homburg/SaarGermany Center for Bioinformatics Saarland Informatics Campus66123 SaarbruckenGermany

Blood-borne small non-coding(snc RNAs)are among the prominent candidates for blood-based diagnostic ***,high-throughput approaches are applied to discover biomarker *** have to be validated in larger cohorts and evaluated by adequate statistical learning ***,we published high-throughput sequencing based microRNA(miRNA)signatures in Alzheimer’s disease(AD)patients in the United States(US)and ***,we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by *** computed models to assess the relation between miRNA expression and phenotypes,gender,age,or disease severity(Mini-Mental State Examination;MMSE).Of the 21 miRNAs,expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts.18 miRNAs were significantly correlated with neurodegeneration(Benjamini-Hochberg adjusted P<0.05)with highest significance for miR-532-5 p(BenjaminiHochberg adjusted P=4.8×10^-30).Machine learning models reached an area under the curve(AUC)value of 87.6%in differentiating AD patients from ***,ten miRNAs were significantly correlated with MMSE,in particular miR-26a/26b-5p(adjusted P=0.0002).Interestingly,the miRNAs with lower abundance in AD were enriched in monocytes and T-helper cells,while those up-regulated in AD were enriched in serum,exosomes,cytotoxic t-cells,and *** study represents the next important step in translational research for a miRNA-based AD test.

关键词： miRNAs Neurodegeneration Alzheimer’s disease Biomarker Non-coding RNAs Gene regulation

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Prediction of and for new environments: What's your model?

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Molecular Plant 2022年第4期15卷 581-582页

作者： hans-peter Piepho University of Hohenheim Institute of Crop ScienceBiostatistics UnitFruwirthstrasse 2370599 StuttgartGermany

Genomic prediction(GP)and genome-wide association studies(GWAS)employ genetic variants(markers)to predict phenotypic performance and identify superior *** plants,due to genotype-environment interaction(GEI),performance is usually assessed across multiple environments,giving rise to phenotypic data matrices with genotypes in rows and environments in columns(Figure 1).The standard approaches to GP and GWAS employ genotype(row)means across environments as a response and analysis focuses on the *** et al.,2022 proposed to apply the same idea using environment(column)means across genotypes as the response and scanning environmental variants for their ability to predict environmental performance.

关键词： environments Figure performance

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Low Energy Certificate——An exploration on optimization and evaluation of energy-efficient building envelope

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Science China(Technological Sciences) 2011年第6期54卷 1639-1644页

作者： ZHANG Hui hans-peter LEIMER School of Architecture Southeast University Nanjing 210096 China Hochschule fuer angewandte Wissenschaft und Kunst Hildesheim 31134 Hildesheim Germany

Energy saving is the crucial task of green architecture,energy-saving design and evaluation should be *** Energy Certificate(LEC),an interactive computer program for energy efficiency and certification of building envelope,is briefly introduced in this paper in aspects of certification standards,procedure,methods *** the evaluation report of Innovation-pavilion PoI features,reference values of LEC are presented.

关键词： optimization and evaluation of energy efficiency Low Energy Certificate(LEC) energy performance of building enve-lope interactive

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Schwann cell Myc-interacting zinc-finger protein 1 without pox virus and zinc finger： epigenetic implications in a peripheral neuropathy

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Neural Regeneration Research 2018年第9期13卷 1534-1537页

作者： David Fuhrmann hans-peter Elsaisser Department of Cytobiology and Cytopathobiology Philipps University of Marburg Marburg Germany

Functionality of adult peripheral nerves essentially relies on differentiation of Schwann cells during post- natal development, as well as fine-tuned re- and transdifferentiation in response to peripheral nerve injury. Epigenetic histone modifications play a major role during the differentiation of embryonic stem cells and diverse organ specific progenitor cells, yet only little is known about the epigenetic regulation of Schwa nn cells. Just recently, Fuhrmann et al. reported how the transcription factor Myc-interacting zinc-finger protein 1 （Mizl） might contribute to Schwann cell differentiation through repression of the histone de- methylase Kdm8. Here, we discuss the potential novel role of Mizl in Schwann cell differentiation and give a short overview about previously reported histone modifications underlying peripheral nerve develop- ment and response to injury.

关键词： Schwann celh differentiation peripheral nerve injury histone methylation epigenetics Mizl

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Drought can favour the growth of small in relation to tall trees in mature stands of Norway spruce and European beech

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Forest Ecosystems 2018年第3期5卷 258-276页

作者： hans Pretzsch Gerhard Schutze peter Biber Center of Life and Food Sciences Weihenstephan Technical University of MunichHans-Carl-von-Carlowitz-Platz 285354 FreisingGermany

Background: Climate change triggered many studies showing that trends and events of environmental conditions can reduce but also accelerate growth at the stand and individual tree level. However, it is still rather unknown how climate change modifies the growth partitioning between the trees in forest ***: Based on long-term girth-tape measurements in mature monospecific and mixed-species stands of Norway spruce(Picea abies(L.) Karst.) and European beech(Fagus sylvatica L.) we traced the effect of the severe droughts in 2003 and 2015 from the stand down to the tree ***: Stand growth of Norway spruce decreased by about 30% in the once-in-a-century drought 2015, while European beech was much more drought resistant. Water availability generally amplified size-asymmetric growth partitioning. Especially in case of Norway spruce water availability primarily fostered the growth of predominant trees, whereas drought favoured the growth of small trees at the expense of the predominant ones. We could not detect significant differences between mixed and monospecific stands in this ***: The drought-induced reallocation of growth in favour of small trees in case of spruce may result from its isohydric character. We hypothesize that as small trees are shaded, they can benefit from the reduced water consumption of their sun-exposed taller neighbours. In case of beech, as an anisohydric species, tall trees suffer less and smaller trees benefit less under drought. The discussion elaborates the consequences of the water dependent growth allocation for forest monitoring, growth modelling, and silviculture.

关键词： Growth partitioning Drought Competition symmetry Climate change Norway spruce European beech

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Numerical Calculation of Monotonicity Properties of the Blow-Up Time of NLS

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Communications in Computational Physics 2009年第2期5卷 745-759页

作者： hans peter Stimming Wolfgang Pauli Institute c/o Institut fur MathematikUniversitat WienBotzmanngasse 91090 WienAustria

We investigate blow-up of the focusing nonlinear Schr¨odinger equation,in the critical and supercritical *** simulations are performed to examine the dependence of the time at which blow-up occurs on properties of the data or the *** cases are considered:dependence on the scale of the nonlinearity when the initial data are fixed;dependence upon the strength of a quadratic oscillation in the initial data when the equation and the initial profile are fixed;and dependence upon a damping factor when the initial data are *** most of these situations,monotonicity in the evolution of the blow-up time does not occur.

关键词： Nonlinear Schr¨odinger equation finite time blow-up wave collapse

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Cathodoluminescence Microscopy of Zircon in HP-and UHPMetamorphic Rocks: A Fundamental Technique for Assessing the Problem of Inclusions versus Pseudo-Inclusions

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Journal of Earth Science 2019年第6期30卷 1095-1107页

作者： hans-peter Schertl Andreas Hertwig Walter VMaresch Institute of Geology Mineralogy and GeophysicsRuhr-University BochumP-44780 BochumGermany College of Earth Science and Engineering Shandong University of Science and TechnologyQingdao 266590China Department of Earth Planetaryand Space SciencesUniversity of CaliforniaLos AngelesCA 90095USA

This paper shows how a faulty approach to the study of mineral inclusions in zircon can lead to misleading interpretations of the geological *** present and discuss two well-documented *** grains separated from HP metamorphic jadeitite of the Rio San Juan Complex,Dominican Republic,and from UHP pyrope quartzite of the Dora Maira Massif,northern Italy,were studied using cathodoluminescence(CL)techniques,in combination with mineral inclusion and age *** general,zircon from both localities shows inherited magmatic core domains with oscillatory zoning and metamorphic *** magmatic cores of zircon from the jadeitite yield ages of 115–117 Ma and host jadeite and omphacite which are of metamorphic origin and formed at about 78 *** from lawsonite blueschist,representing the country rock of the jadeitite,contains domains with oscillatory zoning that are nearly identical in age to the zircon cores from the adjacent jadeitite,and also contains younger metamorphic minerals such as lawsonite,albite,phengite(Si3.68),chlorite,and *** observations were made on the magmatic cores of zircon from the pyrope *** are about 275 Ma in age and host pyrope,phengite(Si3.55),talc,and kyanite,all of which formed during UHP metamorphism at about 35 *** from the biotite-phengite-gneiss country rock(metagranite)shows oscillatory zoning and yields ages that are identical to those of the magmatic cores of zircon from pyrope quartzite,which thus reflect granitic intrusion *** country-rock zircon also encloses metamorphic minerals with ages of about 35 *** minerals are,for example,garnet and phengite,as well as a polymineralic assemblage of clinopyroxene+garnet+phengite+quartz,that point to formation at UHP metamorphic conditions around 40 kbar/750℃.Based on these examples we suggest an effective approach centered on key evidence from CL studies to show that magmatic domains of zircon may actually contain pseudo-inclusions whic

关键词： zircon cathodoluminescence inclusion pseudo-inclusion jadeitite pyrope-quarzite whiteschist

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A goal-based approach to the identification of essential transformation variables in support of the implementation of the 2030 agenda for sustainable development

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International Journal of Digital Earth 2020年第2期13卷 166-187页

作者： hans-peter Plag Shelley-Ann Jules-Plag Department of Ocean Earth and Atmospheric SciencesOld Dominion UniversityNorfolkVAUSA Mitigation and Adaptation Research Institute Old Dominion UniversityNorfolkVAUSA Tiwah UG RossbachGermany Department of Engineering Management and Systems EngineeringOld Dominion UniversityNorfolkVAUSA

The United Nations’2030 Agenda for Sustainable Development sets seventeen Sustainable Development Goals(SDGs)to be achieved by *** observation are needed that can support the development and validation of transformation policies to make progress towards the SDGs.A participatory and inclusive goal-based approach(GBA)is introduced that links societal goals,targets and indicators to Essential Transformation Variables(ETVs)of the human and non-human *** GBA is complementary to the widely used expertbased *** GBA is applied to the SDGs at the goal,target and indicator *** high-level conceptual model used for the SDGs is humanity embedded in the Earth’s life-support system(ELSS).At the goal level,very few of the SDGs are directly focusing on the ELSS and its *** of the SDG Targets focus on transformations in society and the built *** targets that explicitly focus on the physiology of the ELSS would be important for *** of the current indicator measure the built environment and the embedded social *** development requires a functioning ELSS,and to ensure this,complementary indicators that bring environmental aspects to the monitoring of SDG targets are needed.

关键词： 2030 agenda for sustainable development sustainable development goals targets indicators essential variables policy making decision making tranformation science

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