Construction of a global map of human gene expression : the process, tools and analysis

This thesis studies human gene expression space using high throughput gene expression data from DNA microarrays. In molecular biology, high throughput techniques allow numerical measurements of expression of tens of thousands of genes simultaneously. In a single study, this data is traditionally obtained from a limited number of sample types with a small number of replicates. For organism-wide analysis, this data has been largely unavailable and the global structure of human transcriptome has remained unknown. This thesis introduces a human transcriptome map of different biological entities and analysis of its general structure. The map is constructed from gene expression data from the two largest public microarray data repositories, GEO and ArrayExpress. The creation of this map contributed to the development of ArrayExpress by identifying and retrofitting the previously unusable and missing data and by improving the access to its data. It also contributed to creation of several new tools for microarray data manipulation and establishment of data exchange between GEO and ArrayExpress. The data integration for the global map required creation of a new large ontology of human cell types, disease states, organism parts and cell lines. The ontology was used in a new text mining and decision tree based method for automatic conversion of human readable free text microarray data annotations into categorised format. The data comparability and minimisation of the systematic measurement errors that are characteristic to each lab- oratory in this large cross-laboratories integrated dataset, was ensured by computation of a range of microarray data quality metrics and exclusion of incomparable data. The structure of a global map of human gene expression was then explored by principal component analysis and hierarchical clustering using heuristics and help from another purpose built sample ontology. A preface and motivation to the construction and analysis of a global map of human gene expression is given by analysis of two microarray datasets of human malignant melanoma. The analysis of these sets incorporate indirect comparison of statistical methods for finding differentially expressed genes and point to the need to study gene expression on a global level.

Language change as an evolutionary process

In the thesis it is discussed in what ways concepts and methodology developed in evolutionary biology can be applied to the explanation and research of language change. The parallel nature of the mechanisms of biological evolution and language change is explored along with the history of the exchange of ideas between these two disciplines. Against this background computational methods developed in evolutionary biology are taken into consideration in terms of their applicability to the study of historical relationships between languages. Different phylogenetic methods are explained in common terminology, avoiding the technical language of statistics. The thesis is on one hand a synthesis of earlier scientific discussion, and on the other an attempt to map out the problems of earlier approaches in addition to finding new guidelines in the study of language change on their basis. Primarily literature about the connections between evolutionary biology and language change, along with research articles describing applications of phylogenetic methods into language change have been used as source material. The thesis starts out by describing the initial development of the disciplines of evolutionary biology and historical linguistics, a process which right from the beginning can be seen to have involved an exchange of ideas concerning the mechanisms of language change and biological evolution. The historical discussion lays the foundation for the handling of the generalised account of selection developed during the recent few decades. This account is aimed for creating a theoretical framework capable of explaining both biological evolution and cultural change as selection processes acting on self-replicating entities. This thesis focusses on the capacity of the generalised account of selection to describe language change as a process of this kind. In biology, the mechanisms of evolution are seen to form populations of genetically related organisms through time. One of the central questions explored in this thesis is whether selection theory makes it possible to picture languages are forming populations of a similar kind, and what a perspective like this can offer to the understanding of language in general. In historical linguistics, the comparative method and other, complementing methods have been traditionally used to study the development of languages from a common ancestral language. Computational, quantitative methods have not become widely used as part of the central methodology of historical linguistics. After the fading of a limited popularity enjoyed by the lexicostatistical method since the 1950s, only in the recent years have also the computational methods of phylogenetic inference used in evolutionary biology been applied to the study of early language history. In this thesis the possibilities offered by the traditional methodology of historical linguistics and the new phylogenetic methods are compared. The methods are approached through the ways in which they have been applied to the Indo-European languages, which is the most thoroughly investigated language family using both the traditional and the phylogenetic methods. The problems of these applications along with the optimal form of the linguistic data used in these methods are explored in the thesis. The mechanisms of biological evolution are seen in the thesis as parallel in a limited sense to the mechanisms of language change, however sufficiently so that the development of a generalised account of selection is deemed as possibly fruiful for understanding language change. These similarities are also seen to support the validity of using phylogenetic methods in the study of language history, although the use of linguistic data and the models of language change employed by these models are seen to await further development.

Effect of GPS on understanding relationship between mobile map and environment : A field experiment

Objectives: GPS technology enables the visualisation of a map reader s location on a mobile map. Earlier research on the cognitive aspects of map reading identified that searching for map-environment points is an essential element for the process of determining one s location on a mobile map. Map-environment points refer to objects that are visualized on the map and are recognizable in the environment. However, because the GPS usually adds only one point to the map that has a relation to the environment, it does not provide a sufficient amount of information for self-location. The aim of the present thesis was to assess the effect of GPS on the cognitive processes involved in determining one s location on a map. Methods: The effect of GPS on self-location was studied in a field experiment. The subjects were shown a target on a mobile map, and they were asked to point in the direction of the target. In order for the map reader to be able to deduce the direction of the target, he/she has to locate himself/herself on the map. During the pointing tasks, the subjects were asked to think aloud. The data from the experiment were used to analyze the effect of the GPS on the time needed to perform the task. The subjects verbal data was used to assess the effect of the GPS on the number of landmark concepts mentioned during a task (landmark concepts are words referring to objects that can be recognized both on the map and in the environment). Results and conclusions: The results from the experiment indicate that the GPS reduces the time needed to locate oneself on a map. The analysis of the verbal data revealed that the GPS reduces the number of landmark concepts in the protocols. The findings suggest that the GPS guides the subject s search for the map-environment points and narrows the area on the map that must be searched for self-location.