Arnoldo Frigessi

Current benchmarks for long-context reasoning in Large Language Models (LLMs) often blur critical factors like intrinsic task complexity, distractor interference, and task length. To enable more precise failure analysis, we introduce CogniLoad, a novel synthetic benchmark grounded in Cognitive Load Theory (CLT). CogniLoad generates natural-language logic puzzles with independently tunable parameters that reflect CLT's core dimensions: intrinsic difficulty ($d$) controls intrinsic load; distractor-to-signal ratio ($\rho$) regulates extraneous load; and task length ($N$) serves as an operational proxy for conditions demanding germane load. Evaluating 22 SotA reasoning LLMs, CogniLoad reveals distinct performance sensitivities, identifying task length as a dominant constraint and uncovering varied tolerances to intrinsic complexity and U-shaped responses to distractor ratios. By offering systematic, factorial control over these cognitive load dimensions, CogniLoad provides a reproducible, scalable, and diagnostically rich tool for dissecting LLM reasoning limitations and guiding future model development.

The availability of high-quality data has led to tremendous advances in science, technology and society at large, when analysed by means of statistical and machine learning (ML) methods. However, real-world data in many cases cannot be made public to the research community due to privacy restrictions. This impairs progress especially in bio-medical research. Synthetic data can substitute the sensitive real data, as long as they do not disclose private aspects. This has proven to be successful in training downstream ML applications. We propose TVineSynth, a vine copula based synthetic tabular data generator. TVineSynth is designed to balance privacy and utility, using the vine tree structure and its truncation to do the trade-off. Contrary to synthetic data generators that achieve differential privacy (DP) by globally adding noise, TVineSynth performs a controlled approximation of the estimated data generating distribution. Because of this it does not suffer from poor utility of the resulting synthetic data for downstream prediction tasks. TVineSynth introduces a targeted bias into the vine copula model. Combined with the specific tree structure of the vine, this causes the model to zero out privacy-leaking dependencies while relying on those that are beneficial for utility. We theoretically justify how the construction of TVineSynth ensures privacy. When compared to competitor models, with and without DP, TVineSynth achieves a superior privacy-utility balance.

We propose TVineSynth, a vine copula based synthetic tabular data generator, which is designed to balance privacy and utility, using the vine tree structure and its truncation to do the trade-off. Contrary to synthetic data generators that achieve DP by globally adding noise, TVineSynth performs a controlled approximation of the estimated data generating distribution, so that it does not suffer from poor utility of the resulting synthetic data for downstream prediction tasks. TVineSynth introduces a targeted bias into the vine copula model that, combined with the specific tree structure of the vine, causes the model to zero out privacy-leaking dependencies while relying on those that are beneficial for utility. Privacy is here measured with membership (MIA) and attribute inference attacks (AIA). Further, we theoretically justify how the construction of TVineSynth ensures AIA privacy under a natural privacy measure for continuous sensitive attributes. When compared to competitor models, with and without DP, on simulated and on real-world data, TVineSynth achieves a superior privacy-utility balance.

We propose TVineSynth, a vine copula based synthetic tabular data generator, which is designed to balance privacy and utility, using the vine tree structure and its truncation to do the trade-off. Contrary to synthetic data generators that achieve DP by globally adding noise, TVineSynth performs a controlled approximation of the estimated data generating distribution, so that it does not suffer from poor utility of the resulting synthetic data for downstream prediction tasks. TVineSynth introduces a targeted bias into the vine copula model that, combined with the specific tree structure of the vine, causes the model to zero out privacy-leaking dependencies while relying on those that are beneficial for utility. Privacy is here measured with membership (MIA) and attribute inference attacks (AIA). Further, we theoretically justify how the construction of TVineSynth ensures AIA privacy under a natural privacy measure for continuous sensitive attributes. When compared to competitor models, with and without DP, on simulated and on real-world data, TVineSynth achieves a superior privacy-utility balance.

Listen to Nysgjerrige på: neste generasjon maskinlæring from Nysgjerrige Norge. Nysgjerrige Norge - Episode 3: Et dypdykk i kunnskapsdrevet maskinlæring med IntegreatI denne episoden tar Kristopher turen til Nils Henrik Abels hus på Blindern i Oslo for å besøke Integreat Senter for Fremragende Forskning. Vi møter professorene og ekteparet Arnoldo Frigessi og Ingrid Glad, som leder det nyoppstartede senteret. De deler visjoner om fremtidens algoritmer, hvor kunnskap og etikk spiller en nøkkelrolle i utviklingen av kunstig intelligens (KI).Nysgjerrige Norge er en serie fra Norges forskningsråd. Sentre for Fremragende Forskning er en støtteordning til landets fremste vitenskapelige miljøer. Du kan lese mer om støtteordningen her. Serien er produsert av Moose Media. Programleder: Kristopher Schau. Musikk: The Dogs. Abonnér på Nysgjerrige Norge og møt flere av landets fremste vitenskapspersonligheter.

We propose TVineSynth, a vine copula based synthetic tabular data generator, which is designed to balance privacy and utility, using the vine tree structure and its truncation to do the trade-off. Contrary to synthetic data generators that achieve DP by globally adding noise, TVineSynth performs a controlled approximation of the estimated data generating distribution, so that it does not suffer from poor utility of the resulting synthetic data for downstream prediction tasks. TVineSynth introduces a targeted bias into the vine copula model that, combined with the specific tree structure of the vine, causes the model to zero out privacy-leaking dependencies while relying on those that are beneficial for utility. Privacy is here measured with membership (MIA) and attribute inference attacks (AIA). Further, we theoretically justify how the construction of TVineSynth ensures AIA privacy under a natural privacy measure for continuous sensitive attributes. When compared to competitor models, with and without DP, on simulated and on real-world data, TVineSynth achieves a superior privacy-utility balance.

The availability of diverse, high-quality data has led to tremendous advances in science, technology and society at large, when analysed by means of statistical and machine learning (ML) methods. However, real-world data, in many cases, cannot be made public to the research community due to privacy restrictions, obstructing progress, especially in bio- medical research. Synthetic data can substitute the sensitive real data, and as long as they do not disclose private aspects. This has proven to be successful in training downstream ML applications. We propose TVineSynth, a vine copula based synthetic tabular data generator, which is designed to balance privacy and utility, using the vine tree structure and its truncation to do the trade-off. Contrary to synthetic data generators that achieve differential privacy (DP) by globally adding noise, TVineSynth performs a controlled approximation of the estimated data generating distribution, so that it does not suffer from poor utility of the resulting synthetic data for downstream prediction tasks. TVineSynth introduces a targeted bias into the vine copula model that, combined with the specific tree structure of the vine, causes the model to zero out privacy-leaking dependencies while relying on those that are beneficial for utility. Privacy is here measured with membership (MIA) and attribute inference attacks (AIA). Further, we theoretically justify how the construction of TVineSynth ensures AIA privacy under a natural privacy measure for continuous sensitive attributes. When compa red to competitor models, with and without DP, on simulated and on real-world data, TVineSynth achieves a superior privacy-utility balance.

Vaccination was a key intervention in controlling the COVID-19 pandemic globally. In early 2021, Norway faced significant regional variations in COVID-19 incidence and prevalence, with large differences in population density, necessitating efficient vaccine allocation to reduce infections and severe outcomes. This study explored alternative vaccination strategies to minimize health outcomes (infections, hospitalizations, ICU admissions, deaths) by varying regions prioritized, extra doses prioritized, and implementation start time. Using two models (individual-based and meta-population), we simulated COVID-19 transmission during the primary vaccination period in Norway, covering the first 7 months of 2021. We investigated alternative strategies to allocate more vaccine doses to regions with a higher force of infection. We also examined the robustness of our results and highlighted potential structural differences between the two models. Our findings suggest that early vaccine prioritization could reduce COVID-19 related health outcomes by 8% to 20% compared to a baseline strategy without geographic prioritization. For minimizing infections, hospitalizations, or ICU admissions, the best strategy was to initially allocate all available vaccine doses to fewer high-risk municipalities, comprising approximately one-fourth of the population. For minimizing deaths, a moderate level of geographic prioritization, with approximately one-third of the population receiving doubled doses, gave the best outcomes by balancing the trade-off between vaccinating younger people in high-risk areas and older people in low-risk areas. The actual strategy implemented in Norway was a two-step moderate level aimed at maintaining the balance and ensuring ethical considerations and public trust. However, it did not offer significant advantages over the baseline strategy without geographic prioritization. Earlier implementation of geographic prioritization could have more effectively addressed the main wave of infections, substantially reducing the national burden of the pandemic.

Background Given the societal, economic and health costs of COVID-19 non-pharmaceutical interventions (NPI), it is important to assess their effects. Human mobility serves as a surrogate measure for human contacts and compliance with NPI. In Nordic countries, NPI have mostly been advised and sometimes made mandatory. It is unclear if making NPI mandatory further reduced mobility. Aim We investigated the effect of non-compulsory and follow-up mandatory measures in major cities and rural regions on human mobility in Norway. We identified NPI categories that most affected mobility. Methods We used mobile phone mobility data from the largest Norwegian operator. We analysed non-compulsory and mandatory measures with before–after and synthetic difference-in-differences approaches. By regression, we investigated the impact of different NPI on mobility. Results Nationally and in less populated regions, time travelled, but not distance, decreased after follow-up mandatory measures. In urban areas, however, distance decreased after follow-up mandates, and the reduction exceeded the decrease after initial non-compulsory measures. Stricter metre rules, gyms reopening, and restaurants and shops reopening were significantly associated with changes in mobility. Conclusion Overall, distance travelled from home decreased after non-compulsory measures, and in urban areas, distance further decreased after follow-up mandates. Time travelled reduced more after mandates than after non-compulsory measures for all regions and interventions. Stricter distancing and reopening of gyms, restaurants and shops were associated with changes in mobility.

Abstract The Covid-19 pandemic has required most countries to implement complex sequences of non-pharmaceutical interventions, with the aim of controlling the transmission of the virus in the population. To be able to take rapid decisions, a detailed understanding of the current situation is necessary. Estimates of time-varying, instantaneous reproduction numbers represent a way to quantify the viral transmission in real time. They are often defined through a mathematical compartmental model of the epidemic, like a stochastic SEIR model, whose parameters must be estimated from multiple time series of epidemiological data. Because of very high dimensional parameter spaces (partly due to the stochasticity in the spread models) and incomplete and delayed data, inference is very challenging. We propose a state-space formalization of the model and a sequential Monte Carlo approach which allow to estimate a daily-varying reproduction number for the Covid-19 epidemic in Norway with sufficient precision, on the basis of daily hospitalization and positive test incidences. The method was in regular use in Norway during the pandemics and appears to be a powerful instrument for epidemic monitoring and management.

The COVID-19 pandemic is challenging nations with devastating health and economic consequences. The spread of the disease has revealed major geographical heterogeneity because of regionally varying individual behaviour and mobility patterns, unequal meteorological conditions, diverse viral variants, and locally implemented non-pharmaceutical interventions and vaccination roll-out. To support national and regional authorities in surveilling and controlling the pandemic in real-time as it unfolds, we here develop a new regional mathematical and statistical model. The model, which has been in use in Norway during the first two years of the pandemic, is informed by real-time mobility estimates from mobile phone data and laboratory-confirmed case and hospitalisation incidence. To estimate regional and time-varying transmissibility, case detection probabilities, and missed imported cases, we developed a novel sequential Approximate Bayesian Computation method allowing inference in useful time, despite the high parametric dimension. We test our approach on Norway and find that three-week-ahead predictions are precise and well-calibrated, enabling policy-relevant situational awareness at a local scale. By comparing the reproduction numbers before and after lockdowns, we identify spatially heterogeneous patterns in their effect on the transmissibility, with a stronger effect in the most populated regions compared to the national reduction estimated to be 85% (95% CI 78%-89%). Our approach is the first regional changepoint stochastic metapopulation model capable of real time spatially refined surveillance and forecasting during emergencies.

Understanding the spreading process of new products provides valuable knowledge that can be used for effective marketing. The ability to make early prediction of success or failure is a great advantage in innovation processes. Extending current literature in a novel way, we propose a data-driven agent-based methodology that accomplishes this task. Inference and predictions are based on short-time observations of the product adoption history and knowledge of the social network of consumers. We model and predict adoptions at the agent level as driven by unobserved peer-to-peer influence and external factors such as marketing. The method compares interaction between consumers and general campaigns, and quantifies the importance of characteristics of customers and their social relations. Our computationally efficient method is demonstrated by analyzing real data, predicting the process far into the future using data from a short period after launch, and validated by simulation experiments on a true full-scale communication network.

Background: Information about the contagiousness of new SARS-CoV-2 variants, including the alpha lineage, and how they spread in various locations is essential. Country-specific estimates are needed because local interventions influence transmissibility. Methods: We analysed contact tracing data from Oslo municipality, reported from January through February 2021, when the alpha lineage became predominant in Norway and estimated the relative transmissibility of the alpha lineage with the use of Poisson regression. Results: Within households, we found an increase in the secondary attack rate by 60% (95% CI 20–114%) among cases infected with the alpha lineage compared to other variants; including all close contacts, the relative increase in the secondary attack rate was 24% (95% CI −6%−43%). There was a significantly higher risk of infecting household members in index cases aged 40–59 years who were infected with the alpha lineage; we found no association between transmission and household size. Overall, including all close contacts, we found that the reproduction number among cases with the alpha lineage was increased by 24% (95% CI 0%−52%), corresponding to an absolute increase of 0.19, compared to the group of index cases infected with other variants. Conclusion: Our study suggests that households are the primary locations for rapid transmission of the new lineage alpha.

Human mobility plays a major role in the spatial dissemination of infectious diseases. We develop a spatio-temporal stochastic model for influenza-like disease spread based on estimates of human mobility. The model is informed by mobile phone mobility data collected in Bangladesh. We compare predictions of models informed by daily mobility data (reference) with that of models informed by time-averaged mobility data, and mobility model approximations. We find that the gravity model overestimates the spatial synchrony, while the radiation model underestimates the spatial synchrony. Using time-averaged mobility resulted in spatial spreading patterns comparable to the daily mobility model. We fit the model to 2014–2017 influenza data from sentinel hospitals in Bangladesh, using a sequential version of approximate Bayesian computation. We find a good agreement between our estimated model and the case data. We estimate transmissibility and regional spread of influenza in Bangladesh, which are useful for policy planning. Time-averaged mobility appears to be a good proxy for human mobility when modelling infectious diseases. This motivates a more general use of the time-averaged mobility, with important implications for future studies and outbreak control. Moreover, time-averaged mobility is subject to less privacy concerns than daily mobility, containing less temporal information on individual movements

Dynamical downscaling of earth system models is intended to produce high-resolution climate information at regional to local scales. Current models, while adequate for describing temperature distributions at relatively small scales, struggle when it comes to describing precipitation distributions. In order to better match the distribution of observed precipitation over Norway, we consider approaches to statistical adjustment of the output from a regional climate model when forced with ERA-40 reanalysis boundary conditions. As a second step, we try to correct downscalings of historical climate model runs using these transformations built from downscaled ERA-40 data. Unless such calibrations are successful, it is difficult to argue that scenario-based downscaled climate projections are realistic and useful for decision makers. We study both full quantile calibrations and several different methods that correct individual quantiles separately using random field models. Results based on cross-validation show that while a full quantile calibration is not very effective in this case, one can correct individual quantiles satisfactorily if the spatial structure in the data are accounted for. Interestingly, different methods are favoured depending on whether ERA-40 data or historical climate model runs are adjusted.

Learning the structure of a Bayesian Network from multidimensional data is an important task in many situations, as it allows understanding conditional (in)dependence relations which in turn can be used for prediction. Current methods mostly assume a multivariate normal or a discrete multinomial model. A new greedy learning algorithm for continuous non-Gaussian variables, where marginal distributions can be arbitrary, as well as the dependency structure, is proposed. It exploits the regular vine approximation of the model, which is a tree-based hierarchical construction with pair-copulae as building blocks. It is shown that the networks obtainable with our algorithm belong to a certain subclass of chordal graphs. Chordal graphs representations are often preferred, as they allow very efficient message passing and information propagation in intervention studies. It is illustrated through several examples and real data applications that the possibility of using non-Gaussian margins and a nonnon-linear dependency structure outweighs the restriction to chordal graphs.

We investigate how well a suite of regional climate models (RCMs) from the ENSEMBLES project represents the residual spatial dependence of daily precipitation. The study area we consider is a 200 km × 200 km region in south central Norway, with RCMs driven by ERA-40 boundary conditions at a horizontal resolution of approximately 25 km × 25 km. We model the residual spatial dependence with pair-copula constructions, which allows us to assess both the overall and tail dependence in precipitation, including uncertainty estimates. The selected RCMs reproduce the overall dependence rather well, though the discrepancies compared to observations are substantial. All models overestimate the overall dependence in the west-east direction. They also overestimate the upper tail dependence in the north-south direction during winter, and in the west-east direction during summer, whereas they tend to underestimate this dependence in the north-south direction in summer. Moreover, many of the climate models do not simulate the small-scale dependence patterns caused by the pronounced orography well. However, the misrepresented residual spatial dependence does not seem to affect estimates of high quantiles of extreme precipitation aggregated over a few grid boxes. The underestimation of the area-aggregated extreme precipitation is due mainly to the well-known underestimation of the univariate margins for individual grid boxes, suggesting that the correction of RCM biases in precipitation might be feasible.

Climate change will affect the insurance industry. We develop a Bayesian hierarchical statistical approach to explain and predict insurance losses due to weather events at a local geographic scale. The number of weather-related insurance claims is modelled by combining generalized linear models with spatially smoothed variable selection. Using Gibbs sampling and reversible jump Markov chain Monte Carlo methods, this model is fitted on daily weather and insurance data from each of the 319 municipalities which constitute southern and central Norway for the period 1997–2006. Precise out-of-sample predictions validate the model. Our results show interesting regional patterns in the effect of different weather covariates. In addition to being useful for insurance pricing, our model can be used for short-term predictions based on weather forecasts and for long-term predictions based on downscaled climate models.

Association between previous antibiotic use and emergence of antibiotic resistance has been reported for several microorganisms. The relationship has been extensively studied, and although the causes of antibiotic resistance are multi-factorial, clear evidence of antibiotic use as a major risk factor exists. Most studies are carried out in countries with high consumption of antibiotics and corresponding high levels of antibiotic resistance, and currently, little is known whether and at what level the associations are detectable in a low antibiotic consumption environment. We conduct an ecological, retrospective study aimed at determining the impact of antibiotic consumption on antibiotic-resistant Pseudomonas aeruginosa in three hospitals in Norway, a country with low levels of antibiotic use. We construct a sophisticated statistical model to capture such low signals. To reduce noise, we conduct our study at hospital ward level. We propose a random effect Poisson or binomial regression model, with a reparametrisation that allows us to reduce the number of parameters. Inference is likelihood based. Through scenario simulation, we study the potential effects of reduced or increased antibiotic use. Results clearly indicate that the effects of consumption on resistance are present under conditions with relatively low use of antibiotic agents. This strengthens the recommendation on prudent use of antibiotics, even when consumption is relatively low.

The immense increase in availability of genomic scale datasets, such as those provided by the ENCODE and Roadmap Epigenomics projects, presents unprecedented opportunities for individual researchers to pose novel falsifiable biological questions. With this opportunity, however, researchers are faced with the challenge of how to best analyze and interpret their genome-scale datasets. A powerful way of representing genome-scale data is as feature-specific coordinates relative to reference genome assemblies, i.e. as genomic tracks. The Genomic HyperBrowser (http://hyperbrowser.uio.no) is an open-ended web server for the analysis of genomic track data. Through the provision of several highly customizable components for processing and statistical analysis of genomic tracks, the HyperBrowser opens for a range of genomic investigations, related to, e.g., gene regulation, disease association or epigenetic modifications of the genome.

Suppose estimates are available for correlations between pairs of variables but that the matrix of correlation estimates is not positive definite. In various applications, having a valid correlation matrix is important in connection with follow-up analyses that might, for example, involve sampling from a valid distribution. We present new methods for adjusting the initial estimates to form a proper, that is, nonnegative definite, correlation matrix. These are based on constructing certain pseudo-likelihood functions, formed by multiplying together exact or approximate likelihood contributions associated with the individual correlations. Such pseudo-likelihoods may then be maximized over the range of proper correlation matrices. They may also be utilized to form pseudo-posterior distributions for the unknown correlation matrix, by factoring in relevant prior information for the separate correlations. We illustrate our methods on two examples from a financial time series and genomic pathway analysis.

Background Elucidating the exact relationship between gene copy number and expression would enable identification of regulatory mechanisms of abnormal gene expression and biological pathways of regulation. Most current approaches either depend on linear correlation or on nonparametric tests of association that are insensitive to the exact shape of the relationship. Based on knowledge of enzyme kinetics and gene regulation, we would expect the functional shape of the relationship to be gene dependent and to be related to the gene regulatory mechanisms involved. Here, we propose a statistical approach to investigate and distinguish between linear and nonlinear dependences between DNA copy number alteration and mRNA expression. Results We applied the proposed method to DNA copy numbers derived from Illumina 109 K SNP-CGH arrays (using the log R values) and expression data from Agilent 44 K mRNA arrays, focusing on commonly aberrated genomic loci in a collection of 102 breast tumors. Regression analysis was used to identify the type of relationship (linear or nonlinear), and subsequent pathway analysis revealed that genes displaying a linear relationship were overall associated with substantially different biological processes than genes displaying a nonlinear relationship. In the group of genes with a linear relationship, we found significant association to canonical pathways, including purine and pyrimidine metabolism (for both deletions and amplifications) as well as estrogen metabolism (linear amplification) and BRCA-related response to damage (linear deletion). In the group of genes displaying a nonlinear relationship, the top canonical pathways were specific pathways like PTEN and PI13K/AKT (nonlinear amplification) and Wnt(B) and IL-2 signalling (nonlinear deletion). Both amplifications and deletions pointed to the same affected pathways and identified cancer as the top significant disease and cell cycle, cell signaling and cellular development as significant networks. Conclusions This paper presents a novel approach to assessing the validity of the dependence of expression data on copy number data, and this approach may help in identifying the drivers of carcinogenesis.

Climate change will affect the insurance industry. We develop a Bayesian hierarchical statistical approach to explain and predict insurance losses due to weather events at a local geographical scale. The number of weather-related insurance claims is modelled combining generalized linear models with spatially smoothed variable selection. Using Gibbs sampling and reversible jump MCMC, the model is fitted on daily weather and insurance data from each of the 319 municipalities of southern and central Norway for the period 1997-2006. Out-of-sample predictions from the model are very good. Our results show interesting regional patterns in the impact of different weather covariates. In addition to being useful for insurance pricing, our model can be used for short-term predictions based on weather forecasts and long-term predictions based on downscaled climate models.

Background: With the recent advances and availability of various high-throughput sequencing technologies, data on many molecular aspects, such as gene regulation, chromatin dynamics, and the three-dimensional organization of DNA, are rapidly being generated in an increasing number of laboratories. The variation in biological context, and the increasingly dispersed mode of data generation, imply a need for precise, interoperable and flexible representations of genomic features through formats that are easy to parse. A host of alternative formats are currently available and in use, complicating analysis and tool development. The issue of whether and how the multitude of formats reflects varying underlying characteristics of data has to our knowledge not previously been systematically treated. Results: We here identify intrinsic distinctions between genomic features, and argue that the distinctions imply that a certain variation in the representation of features as genomic tracks is warranted. Four core informational properties of tracks are discussed: gaps, lengths, values and interconnections. From this we delineate fifteen generic track types. Based on the track type distinctions, we characterize major existing representational formats and find that the track types are not adequately supported by any single format. We also find, in contrast to the XML formats, that none of the existing tabular formats are conveniently extendable to support all track types. We thus propose two unified formats for track data, an improved XML format, BioXSD 1.1, and a new tabular format, GTrack 1.0. Conclusions: The defined track types are shown to capture relevant distinctions between genomic annotation tracks, resulting in varying representational needs and analysis possibilities. The proposed formats, GTrack 1.0 and BioXSD 1.1, cater to the identified track distinctions and emphasize preciseness, flexibility and parsing convenience.

Background Transcription factors in disease-relevant pathways represent potential drug targets, by impacting a distinct set of pathways that may be modulated through gene regulation. The influence of transcription factors is typically studied on a per disease basis, and no current resources provide a global overview of the relations between transcription factors and disease. Furthermore, existing pipelines for related large-scale analysis are tailored for particular sources of input data, and there is a need for generic methodology for integrating complementary sources of genomic information. Results We here present a large-scale analysis of multiple diseases versus multiple transcription factors, with a global map of over-and under-representation of 446 transcription factors in 1010 diseases. This map, referred to as the differential disease regulome, provides a first global statistical overview of the complex interrelationships between diseases, genes and controlling elements. The map is visualized using the Google map engine, due to its very large size, and provides a range of detailed information in a dynamic presentation format. The analysis is achieved through a novel methodology that performs a pairwise, genome-wide comparison on the cartesian product of two distinct sets of annotation tracks, e.g. all combinations of one disease and one TF. The methodology was also used to extend with maps using alternative data sets related to transcription and disease, as well as data sets related to Gene Ontology classification and histone modifications. We provide a web-based interface that allows users to generate other custom maps, which could be based on precisely specified subsets of transcription factors and diseases, or, in general, on any categorical genome annotation tracks as they are improved or become available. Conclusion We have created a first resource that provides a global overview of the complex relations between transcription factors and disease. As the accuracy of the disease regulome depends mainly on the quality of the input data, forthcoming ChIP-seq based binding data for many TFs will provide improved maps. We further believe our approach to genome analysis could allow an advance from the current typical situation of one-time integrative efforts to reproducible and upgradable integrative analysis. The differential disease regulome and its associated methodology is available at http://hyperbrowser.uio.no

The immense increase in the generation of genomic scale data poses an unmet analytical challenge, due to a lack of established methodology with the required flexibility and power. We propose a first principled approach to statistical analysis of sequence-level genomic information. We provide a growing collection of generic biological investigations that query pairwise relations between tracks, represented as mathematical objects, along the genome. The Genomic HyperBrowser implements the approach and is available at http://hyperbrowser.uio.no.

Background Oligoarrays have become an accessible technique for exploring the transcriptome, but it is presently unclear how absolute transcript data from this technique compare to the data achieved with tag-based quantitative techniques, such as massively parallel signature sequencing (MPSS) and serial analysis of gene expression (SAGE). By use of the TransCount method we calculated absolute transcript concentrations from spotted oligoarray intensities, enabling direct comparisons with tag counts obtained with MPSS and SAGE. The tag counts were converted to number of transcripts per cell by assuming that the sum of all transcripts in a single cell was 5·105. Our aim was to investigate whether the less resource demanding and more widespread oligoarray technique could provide data that were correlated to and had the same absolute scale as those obtained with MPSS and SAGE. Results A number of 1,777 unique transcripts were detected in common for the three technologies and served as the basis for our analyses. The correlations involving the oligoarray data were not weaker than, but, similar to the correlation between the MPSS and SAGE data, both when the entire concentration range was considered and at high concentrations. The data sets were more strongly correlated at high transcript concentrations than at low concentrations. On an absolute scale, the number of transcripts per cell and gene was generally higher based on oligoarrays than on MPSS and SAGE, and ranged from 1.6 to 9,705 for the 1,777 overlapping genes. The MPSS data were on same scale as the SAGE data, ranging from 0.5 to 3,180 (MPSS) and 9 to1,268 (SAGE) transcripts per cell and gene. The sum of all transcripts per cell for these genes was 3.8·105 (oligoarrays), 1.1·105 (MPSS) and 7.6·104 (SAGE), whereas the corresponding sum for all detected transcripts was 1.1·106 (oligoarrays), 2.8·105 (MPSS) and 3.8·105 (SAGE). Conclusion The oligoarrays and TransCount provide quantitative transcript concentrations that are correlated to MPSS and SAGE data, but, the absolute scale of the measurements differs across the technologies. The discrepancy questions whether the sum of all transcripts within a single cell might be higher than the number of 5·105 suggested in the literature and used to convert tag counts to transcripts per cell. If so, this may explain the apparent higher transcript detection efficiency of the oligoarrays, and has to be clarified before absolute transcript concentrations can be interchanged across the technologies. The ability to obtain transcript concentrations from oligoarrays opens up the possibility of efficient generation of universal transcript databases with low resource demands.

Infectious salmon anemia (ISA) is one of the main infectious diseases in Atlantic salmon farming with major economical implications. Despite the strong regulatory interventions, the ISA epidemic is not under control, worldwide. We study the data covering salmon farming in Norway from 2002 to 2005 and propose a stochastic space-time model for the transmission of the virus. We model seaway transmission between farm sites, transmission through shared management and infrastructure, biomass effects and other potential pathways within the farming industry. We find that biomass has an effect on infectiousness, the local contact network and seaway distance of 5 km represent similar risks, but a large component of risk originates from other sources, among which are possibly infected salmon smolt and boat traffic.