Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology : a GWAS-based study using the Allen Human Brain Atlas

Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.Peer reviewe

Transfer and templates in scientific modeling

The notion of (computational) template has recently been discussed in relation to cross-disciplinary transfer of modeling efforts and in relation to the representational content of models. We further develop and disambiguate the notion of template and find that, suitably developed, it is useful in distinguishing and analyzing different types of transfer, none of which supports a non-representationalist view of models. We illustrate our main findings with the modeling of technology substitution with Lotka-Volterra Competition equations

Transfer and templates in scientific modelling

The notion of template has been advocated by Paul Humphreys and others as an illuminating unit of analysis in the philosophy of scientific modelling. Templates are supposed to have the dual functions of representing target systems and of facilitating quantitative manipulation. A resulting worry is that wide-ranging cross-disciplinary use of templates might compromise their representational function and reduce them to mere formalisms. In this paper, we argue that templates are valuable units of analysis in reconstructing cross-disciplinary modelling. Central to our discussion are the ways in which Lotka-Volterra models are used to analyse processes of technology diffusion. We illuminate both the similarities and differences between contributions to this case of cross-disciplinary modelling by reconstructing them as transfer of a template, without reducing the template to a mere formalism or a computational model. This requires differentiating the interpretation of templates from that of the models based on them. This differentiation allows us to claim that the LV models of technology diffusion that we review are the result of template transfer - conformist in some contributions, creative in others

Belief Revision and Verisimilitude Based on Preference and Truth Orderings

In this rather technical paper we establish a useful combination of belief revision and verisimilitude according to which better theories provide better predictions, and revising with more verisimilar data results in theories that are closer to the truth. Moreover, this paper presents two alternative definitions of refined verisimilitude, which are more perspicuous than the algebraic version used in previous publications.