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  • 1.
    Bondesson, Lennart
    et al.
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Fahlén, Jessica
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Mean and variance of vacancy for hard-core Disc processes and applications2003In: Scandinavian Journal of Statistics, ISSN 0303-6898, E-ISSN 1467-9469, Vol. 30, no 4, p. 797-816Article in journal (Refereed)
  • 2.
    Eriksson, Kåre
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Liljelind, Ingrid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Fahlén, Jessica
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Lampa, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Should styrene be sampled on the left or right shoulder?: An important question in employee self-assessment.2005In: Annals of Occupational Hygiene, ISSN 0003-4878, E-ISSN 1475-3162, Vol. 49, no 6, p. 529-533Article in journal (Refereed)
    Abstract [en]

    A self-operated personal sampling technique called 'self assessment of exposure' (SAE) has been suggested as an easy method for collecting inhalation exposure data, as the workers themselves are performing the sampling. Employers and employees have raised the question of whether a different estimate of the air concentration is likely to be obtained depending on whether the sampler is fastened at the left or the right shoulder. In order to answer this question, the exposure to styrene vapour in two different small enterprises within the reinforced plastics industry was measured. Seven workers participated and the air sampling was performed by diffusive sampling. We observed no statistically significant difference in the determined air concentration of styrene between the left and right shoulder (P = 0.878). The results strongly indicate that the fastening of a sampler on the left or right shoulder does not produce a difference in the estimation of the inhalation exposure. SAE can thus be used to collect reliable exposure data of styrene vapour. The reliability of SAE will most certainly inspire occupational hygienists, physicians and other experts to involve the workers in repeated exposure measurements. Taking the exposure variability into account, repeated measurements are crucial when evaluating acute and chronic health effects following inhalation exposure to gases and vapours from chemical hazards.

  • 3.
    Fahlén, Jessica
    Umeå University, Faculty of Science and Technology, Mathematical statistics.
    Coverage problems for Strauss disc processes2001Licentiate thesis, monograph (Other academic)
  • 4.
    Fahlén, Jessica
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Essays on spatial point processes and bioinformatics2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis consists of two separate parts. The first part consists of one paper and considers problems concerning spatial point processes and the second part includes three papers in the field of bioinformatics.

    The first part of the thesis is based on a forestry problem of estimating the number of trees in a region by using the information in an aerial photo, showing the area covered by the trees. The positions of the trees are assumed to follow either a binomial point process or a hard-core Strauss process. Furthermore, discs of equal size are used to represent the tree-crowns. We provide formulas for the expectation and the variance of the relative vacancy for both processes. The formulas are approximate for the hard-core Strauss process. Simulations indicate that the approximations are accurate. 

    The second part of this thesis focuses on pre-processing of microarray data. The microarray technology can be used to measure the expression of thousands of genes simultaneously in a single experiment. The technique is used to identify genes that are differentially expressed between two populations, e.g. diseased versus healthy individuals. This information can be used in several different ways, for example as diagnostic tools and in drug discovery.

    The microarray technique involves a number of complex experimental steps, where each step introduces variability in the data. Pre-processing aims to reduce this variation and is a crucial part of the data analysis. Paper II gives a review over several pre-processing methods. Spike-in data are used to describe how the different methods affect the sensitivity and bias of the experi­ment.

    An important step in pre-processing is dye-normalization. This normalization aims to re­move the systematic differences due to the use of different dyes for coloring the samples. In Paper III a novel dye-normalization, the MC-normalization, is proposed. The idea behind this normaliza­tion is to let the channels’ individual intensities determine the cor­rection, rather than the aver­age intensity which is the case for the commonly used MA-normali­zation. Spike-in data showed that  the MC-normalization reduced the bias for the differentially expressed genes compared to the MA-normalization.

    The standard method for preserving patient samples for diagnostic purposes is fixation in formalin followed by embedding in paraffin (FFPE). In Paper IV we used tongue-cancer micro­RNA-microarray data to study the effect of FFPE-storage. We suggest that the microRNAs are not equally affected by the storage time and propose a novel procedure to remove this bias. The procedure improves the ability of the analysis to detect differentially expressed microRNAs.

  • 5.
    Fahlén, Jessica
    et al.
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Landfors, Mattias
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Freyhult, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Bylesjö, Max
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Bioinformatics strategies for cDNA-microarray data processing2009In: Batch effects and noise in microarray experiments: sources and solutions / [ed] Scherer, Andreas, Wiley and Sons , 2009, 1, , p. 272p. 61-74Chapter in book (Other academic)
    Abstract [en]

    

    Pre-processing plays a vital role in cDNA-microarray data analysis. Without proper pre-processing it is likely that the biological conclusions will be misleading. However, there are many alternatives and in order to choose a proper pre-processing procedure it is necessary to understand the effect of different methods. This chapter discusses several pre-processing steps, including image analysis, background correction, normalization, and filtering. Spike-in data are used to illustrate how different procedures affect the analytical ability to detect differentially expressed genes and estimate their regulation. The result shows that pre-processing has a major impact on both the experiment’s sensitivity andits bias. However, general recommendations are hard to give, since pre-processing consists of several actions that are highly dependent on each other. Furthermore, it is likely that pre-processing have a major impact on downstream analysis, such as clustering and classification, and pre-processing methods should be developed and evaluated with this in mind.

  • 6.
    Fahlén, Jessica
    et al.
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Rentoft, Matilda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    MicroRNA-microarray data analysis in the precence of FFPE storage time effects2010Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The standard method for preserving patient samples for diagnostic purposes is fixation in formalin followed by embedding in paraffin (FFPE). The use of FFPE blocks makes it possible to include a large number of patients in the experimental studies since millions of FFPE blocks are stored around the world. However, FFPE storage can cause degradation and modifi­cations of nucleic acids. In order to draw reliable biological conclusions it is therefore important to know what effect FFPE-storage have on the tissues and to have procedures that normalize this effect. In this paper, we study the effect that FFPE-storage has on microRNA-microarray data from tongue-cancer patients and propose a novel procedure for normalizing the bias intro­duced by FFPE-storage.

    Results: MicroRNA-microarray data from 21 tongue-cancer patients and 8 control patients were used. The samples were stored in FFPE blocks and had been in storage for up to 11 years. The data contained a large amount of biological relevant variation, yet the largest variation was due to the samples storage times. The storage effect was shown to be significant and some results suggested that it may be causal. Moreover, the microRNAs were unequally affected by storage and this could partially be explained by sequence characteristics. The novel normaliza­tion procedure was shown to have a large impact in the analysis ability to identify differentially expressed microRNAs between young and old cancer patients as well as between cancer and control patients. The p-values for the top microRNAs candidates were much lower for the pro­posed novel normalization compared to a standard normalization procedure which suggested that the novel normalization made the analysis more efficient.

    Conclusions: MicroRNA-microarray data can be seriously affected by FFPE-storage and the introduced variation cannot be removed by standard normalizations. The proposed normaliza­tion removes the bias introduced by FFPE-storage and gives higher sensitivity than the standard normalization.

  • 7.
    Fahlén, Jessica
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Wiberg, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    KU-dag som möjlighet till erfarenhetsutbyte2016Conference paper (Refereed)
    Abstract [sv]

    Många lärare på högskolor och universitet har kompetensutveckling (KU) i sin tjänst vilket är reglerade i lokala avtal. Enligt Umeå universitets avtal innebär det att alla universitetslektorer ska under en treårs period ges utrymme om minst 20 procent. Vidare framgår att avrapporteringen av genomförda uppgifter ska ske på lämpligt sätt. Avstämning och revidering av lärarens kompetensutvecklingsplan sker vanligtvis på de flesta institutionerna/enheterna vid återkommande utvecklingssamtal. På vår Enhet har det vanliga varit har lärarna har genomfört sin KU utifrån sin plan och rapporterat en gång per år vid utvecklingssamtalet. Vid detta tillfälle har även planen reviderats. Tyvärr sker då inte ett erfarenhetsutbyte mellan kollegor utan enbart en avrapportering mot närmaste chef. För att förändra det här införde vi för tre år sedan på försök en KU-dag. Inspirationen till en KU-dag kom från Enhetens doktoranddag som ges en gång per år och där alla doktorander presenterar vad de har gjort det gångna året samt blickar framåt vad de ska göra det kommande året. Idén med en KU-dag är att alla som har KU-tid i sin bemanning presenterar vad de har gjort på sin tid samt en kort framåtblick på 10-15 minuter. För att engagera fler personer att delta så uppmanade vi även alla projektledare med externa medel att presentera vad de gör på sin forskningstid. Vårt huvudsakliga syfte med KU-dagen var att synliggöra vad alla gör samt att öppna upp för att lära oss av varandra men också för att öka medvetenheten om vad alla gör på Enheten. Erfarenheterna efter tre år med en årlig KU-dag har varit många. Första året så upplevde vi en viss osäkerhet bland deltagarna. Vad leder egentligen införandet av en KU-dag till? Är den till för att kontrollera ens arbete eller kan man lära sig något? Redan andra året så uttryckte flera av deltagarna att de ville delta och det pratades om det i positiva termer både inför och efter genomförandet. Detta beror troligtvis på att vi arbetat aktivt med att det inte ska kännas som en kontroll utan mer till för att dela erfarenheter. Nu efter att ha genomfört det ett tredje år så ses det som ett självklart inslag i vår verksamhet. Lärdomar vi har dragit under de här åren inkluderar betydelsen av hur man lanserar KU-dagen, när på terminen den ges för att säkerställa att så många som möjligt kan delta, samt hur värdefullt det är att vara medveten om vad andra gör för att skapa nya projekt och ett inkluderande arbetsklimat på Enheten.

  • 8.
    Landfors, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Fahlén, Jessica
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Rydén, Patrik
    Umeå University, Faculty of Social Sciences, Department of Statistics. Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    MC-normalization: a novel method for dye-normalization of two-channel microarray data2009In: Statistical Applications in Genetics and Molecular Biology, ISSN 1544-6115, E-ISSN 1544-6115, Vol. 8, no 1, p. 42-Article in journal (Refereed)
    Abstract [en]

    Motivation: Pre-processing plays a vital role in two-color microarray data analysis. An analysis is characterized by its ability to identify differentially expressed genes (its sensitivity) and its ability to provide unbiased estimators of the true regulation (its bias). It has been shown that microarray experiments regularly underestimate the true regulation of differentially expressed genes. We introduce the MC-normalization, where C stands for channel-wise normalization, with considerably lower bias than the commonly used standard methods.

    Methods: The idea behind the MC-normalization is that the channels’ individual intensities determine the correction, rather than the average intensity which is the case for the widely used MA-normalization. The two methods were evaluated using spike-in data from an in-house produced cDNA-experiment and a public available Agilent-experiment. The methods were applied on background corrected and non-background corrected data. For the cDNA-experiment the methods were either applied separately on data from each of the print-tips or applied on the complete array data. Altogether 24 analyses were evaluated. For each analysis the sensitivity, the bias and two variance measures were estimated.

    Results: We prove that the MC-normalization has lower bias than the MA-normalization. The spike-in data confirmed the theoretical result and suggest that the difference is significant. Furthermore, the empirical data suggest that the MC-and MA-normalization have similar sensitivity. A striking result is that print-tip normalizations did have considerably higher sensitivity than analyses using the complete array data.

  • 9.
    Rentoft, Matilda
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Fahlén, Jessica
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Coates, PJ
    Laurell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    miRNA analysis of formalin-fixed squamous cell carcinomas of the tongue is affected by age of the samples2011In: International Journal of Oncology, ISSN 1019-6439, Vol. 38, no 1, p. 61-69Article in journal (Refereed)
    Abstract [en]

    Global miRNA expression arrays were used for analysis of 836 miRNAs in formalin-fixed paraffin-embedded samples from 21 tongue cancer patients and 8 controls. Samples had been stored for one to eleven years. Results separated tumour samples from controls, however, the largest variation was correlated to sample storage time, detectable already after one year. With the use of a linear regression model we could adjust for the storage-dependent effect, leading to the identification of 54 differentially expressed miRNAs in tongue cancer, compared to 16 when using standard normalization, including up-regulation of a novel miRNA, miR-424.

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