Research Director
Lars Holden
- Department ADMIN
- Mobile phone 91175642
- Phone number 22852672
- E-mail holden@nr.stage.dekodes.no
Show description information
Hide description information
Lars Holden is a research director.
Holden was managing director at the Norwegian Computing Center between 2001 and 2022. He has had a central role in the development of the Norwegian research sector and national research policies, founding the Association of Norwegian Research Institutes (FFA) in 2009, and as chairman of the board between 2009 and 2023. He has founded two private companies based on his own research and been a part-time professor in applied mathematics at University of Oslo. He has written more than 50 scientific articles in mathematics, both theory and with applications including geology, gene technology, biology, finance and history, and he is still an active researcher.
Holden is a member of the Norwegian Academy of Technological Sciences, NTVA.
Education
- 1983 – Cand. Scient, numerical analysis, University of Oslo
- 1990 – Dr. Philos, mathematics, University of Oslo
Work experience
Norsk Regnesentral
- 2022 – Research director
- 2001 – 2022 Managing director (CEO)
- 1990 – 2001 Research director
- 1984 – 1989 Research scientist
- 1995 – 1997 Professor, part-time, applied mathematics, University of Oslo
Administrative chairs
- Chairman of board, Association of Research institutes in Norway (all institutes) 2009-
- Member of board, Forum for technical-industrial research institutes, 2009-
- Member of committee for cooperation between universities, university colleges and research institutes, member 2009-, chair 2011 and every second year.
- Member of board, Portfolio of enabling technologies, Research Council of Norway, 2019-
- Member of board, Division of Innovation, Research Council of Norway, 2013-2018
- Vicechairman of board, Norwegian Institutes for Air Research 2012-2018
- Member of board, Kunnskap Oslo, 2009-2012, Deputy member 2012-2014
- Chairman of board, Forskning.no. deputy 2006-2007, member, 2007-2010, chair 2010-2015
- Member of board, Industrial Council, Norwegian Academy of Technical Science, 2007-2015
- Member of board, Simula Research Laboratory, 2001-2005.
- Deputy member of board, Geomatic, 1995-1996.
- Co-founder and Deputy member of the board, Odin Reservoir Software & Services, 1992-1993
- Co-founder and Member of the board, Technical Software Consultants a.s.,1988-1995.
- Member of the board NR, 1986-1989, Representative for the employees.
- Chairman of the union of employees at NR (FANR), 1985-1986.
- Member of Norwegian Mathematical Council, Representative from NR in 1984 and 1985.
- Editorial work: Assistant editor in Mathematical Geology, 1998-2007.
- Member of organizing committee of 9 international conferences.
Entrepreneurship
I was one of the founders of Technical Software Consultants AS which was established in 1988, and Odin Reservoir Software & Services, established in 1992. Both companies were bought by large international companies and the ideas we developed are still in use in the oil industry.
Academy
Elected member of Norwegian Academy of Technical Science
Scientific presentations
- More than 50 journal papers
- More than 50 scientific presentations at international conferences
- More than 20 presentations on research politics at national conferences
- Supervision of PhD students: 5 candidates
Academic book
Hegna, Håvard; Holden, Lars. Norsk Regnesentral 1952-2002 (NRs historie). 2002 pp 392.
Projects
Publications
- 379 publications found
Gavriluk, Oxana; Snapkow, Igor; Thalabard, Jean-Christophe; Holden, Lars; Holden, Marit; Bøvelstad, Hege Marie og Lund, Eiliv. (2026).
Gene Expression Profiling of Peripheral Blood and Endometrial Cancer Risk Factors: Systems Epidemiology Approach in the NOWAC Postgenome Cohort Study.
Vis sammendrag
ntroduction: The increasing incidence of endometrial cancer (EC) requires an extensive search for novel preventive tools and early intervention approaches. However, the development of reliable predictive models is impossible without knowledge of genetic alterations prior to diagnosis. In this work, we aimed to establish whether known EC risk factors are associated with peripheral blood gene expression changes in a prospective design and whether such associations differ between women who later developed EC and matched controls. Methods: First, we selected variables (parity status, lifetime number of years of menstruation, coffee consumption, body mass index (BMI), age at menopause, use of oral contraceptives) that were shown to have an impact on EC risk in a large prospective cohort (165,000 women). Next, using BeadChip microarray technology, we tested the association between these variables and gene expression profiles in RNA extracted from mixed circulating immune cells in a nested case-control study (79 case-control pairs) of women from the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis (GSEA). Results: At overall gene expression level, we found no difference between the EC cases and controls. The introduction of parity status into the statistical model revealed changes in the expression of 1,379 genes in the controls, while we did not observe any expression changes in the cases. Twenty-seven genes were associated with BMI increase in the controls, whereas there was no association observed between changes in BMI and gene expression in women with EC. In GSEA, 2,407 significantly enriched gene sets were attributed to a parity increase among cancer-free women. Conclusion: In this study, we found that an increased number of parities has a life-long effect on the gene expression profile in the peripheral blood of women who never developed cancer. In contrast, in women who were diagnosed with EC later in life, neither multiparity nor elevated BMI showed a significant association with gene expression patterns. However, given the modest sample size and exploratory nature of the study, these findings should be verified in larger cohorts.
Vollestad, John Enok; Holden, Lars og Løland, Anders. (2026).
Personopplysninger i forskningsprosjekter ved Norsk Regnesentral, 2025.
NVA
Rapport
Vis sammendrag
Dette er en oppdatering av notat ADMIN/1/19 der Erik Vasaasen var medforfatter. Hensikten med dette dokumentet er å dokumentere rutinene for behandling av sensitive personopplysninger i NRs forskningsprosjekter i tråd med NRs rutiner for internkontroll. Det sentrale formålet er å fastlegge hvem som er ansvarlig for hva når personopplysninger skal håndteres.
Dokumentet inneholder det som kreves etter Personopplysningsloven, med siste oppdatering i juni 2021 som inkorporerer EUs regelverk GDPR.
Holden, Lars. (2026).
Norwegian Historical Population Register. University of Oslo Library
NVA
Vitenskapelig foredrag
Holden, Lars; Boudko, Svetlana og Fjellvoll, Bjørn. (2025).
Historisk befolkningsregister som et autoritetsregister for personer og verktøy for lokalhistorisk forskning.
Vis sammendrag
Historisk befolkningsregister (HBR) er et autoritetsregister over alle personene i norsk personhistorisk kildemateriale tilbake til 1801 og gjør det mulig å identifisere og gjenfinne personene i disse kildene. Hver person får en unik ID som er viktig for dokumentasjon og for å finne mer informasjon om vedkommende. HBR utvider perioden med detaljert kunnskap om hver person i den norske befolkningen fra 60 år i dagens folkeregister til 224 år, fra to til syv generasjoner. I denne artikkelen beskriver vi oppbyggingen av HBR med lenkingsstrategier samt personvern og hvordan det avviker fra andre befolkningsoversikter. Videre blir det drøftet hvordan man kan oppnå best mulig kvalitet i registeret, samt representativitet og hvor høy lenkingsgrad det er mulig å oppnå. Kunnskap om hver enkelt persons livsløp, bosted og familie gir en ny innsikt i befolkningen og åpner for nye forskningsmetoder og mer presise beskrivelser og analyser. Dette vises ved å gi et datagrunnlag for migrasjon 1910–1920 og en analyse av fødselsdatoer i folketellinger. Forskere vil kunne trekke ut data om de problemstillinger de interesserer seg for, som grunnlag for sin egen forskning.
Holden, Helge og Holden, Lars. (2025).
Optimal rebalancing strategies reduce market variability.
Vis sammendrag
The increasing fraction of passive funds influences stock market variability since passive investors behave differently than active investors. We demonstrate via simulations how portfolios that rebalance between different classes of assets influence the market variability. We prove that the optimal strategy for such portfolios when we include transaction costs, is only to rebalance when the portfolio leaves a no-trade region in the state space. This is the case also when the expectation and volatility of the prices are inhomogeneous. We show that portfolios that apply an optimal rebalance strategy reduce the variability in the stock market measured in the sum of the distances between local minimum and maximum of the prices in the stock market, also when these portfolios constitute only a small part of the market. However, the more usual rebalance strategies that only consider to rebalance at the end of a month or a quarter, have a much weaker influence on the market variability.
Lund, Eiliv; Busund, Lill-Tove Rasmussen og Holden, Lars. (2025).
Curvilinear incidence models for parity in the entire fertility range for cancers of the breast, ovary, and endometrium: A follow-up of the Norwegian 1960 Census.
Vis sammendrag
The protective effect of parity has been demonstrated for cancer of the breast, ovary, and endometrium but no studies have estimated the effect of each subsequent birth in women with 10 or more children or grand-grand parity women, nor compared the linear relationship of the three cancers sites. Here, we aim to explore these relationships based on the Norwegian 1960 Census. The question of parity in present marriage was answered by 385,816 women born 1870–1915, a period with high fertility. Age at marriage has been validated as a proxy for age at first birth AFB. With high parity age at first birth will logically be restricted to early births giving structural zeros. Follow-up was based on linkages to national registers until the first of any of the three diagnoses, death, or age 90 before 31.12.2005. Included were 16,905 breast cancers, 3827 ovarian cancers, and 3834 endometrial cancers. Age- and period-specific incidence rates based on person-years, PY, were used in logit regression models. The percentage decrease for each additional child over the total parity range was for breast cancer 10.5% (95% CI; 9.6–11.4), ovarian cancer 13.2% (11.2–15.3), and endometrial cancer 10.9% (8.9–12.8), in a model without higher order terms. Adjustment for structural zeros reduced the effect of age at first birth to less than one additional child. To the best of our knowledge this is the first analysis of the curvilinear relationships for cancers of the breast, ovary, and endometrium throughout the extended fertility range.
Gabrielsen, Ane Møller; Ostrop, Jenny; Kvale, Live Håndlykken; Holden, Lars; Dagslott, Nenitha Charlotte og Klokkerud, Trine Pernille. (2024).
Sluttrapport- Anbefaling til nasjonal fellesløsning for datahåndteringsplanlegging (DMP).
NVA
Rapport
Holden, Lars. (2024).
Folkeforskning mellom maskiner og hoder. Nasjonalbiblioteket
NVA
Faglig foredrag
Gabrielsen, Ane Møller; Ostrop, Jenny; Kvale, Live Håndlykken; Holden, Lars; Dagslott, Nenitha Charlotte og Klokkerud, Trine Pernille. (2024).
Sluttrapport- Anbefaling til nasjonal fellesløsning for datahåndteringsplanlegging (DMP).
Vis sammendrag
Sluttrapport fra en arbeidsgruppe initiert av Sikt som hadde som formål å gi en anbefaling på hvilket datahåndteringsplanverktøy som bør tilbys som en nasjonal fellesløsning i Norge. Arbeidsgruppen besto av representranter fra Universitets- og Høgskolerådet (UHR), Forskningsinstituttenes fellesarena (FFA), Norges Forskningsråd (NFR), Sigma2 og Sikt- kunnskapssektorens tjenesteleverandør. Rapporten skisserer brukerbehov og behov for funskjonalitet i et datahåndteringsplanverktøy og ser dette opp mot to internasjonale verktøy, DMP online og Data Stewardship Wizard (DSW) sammen med en anbefaling av hvilket som i best mulig grad møter brukerbehov og funksjonalitet. Rapporten gir videre anbefalinger rundt hvem som bør drifte og vedlikeholde en teknisk instans og hvordan oppfølgning av maler, veiledninger og støtte til bruk av verktøy bør organiseres og finansieres.
Holden, Lars. (2023).
En stat som bruker forskning til å ta beslutninger i kriser. FFA
NVA
Faglig foredrag
Holden, Lars; Skoie, Mathilde; Røeggen, Vidar og Bakke, Pål. (2023).
Hvordan ønsker vi at et fremtidig publiseringslandskap skal se ut?
NVA
Leserinnlegg
Bævre, Kåre; Holden, Lars; Lyngstad, Torkild Hovde og Modalsli, Jørgen. (2023).
Helsestatistikk i fare.
NVA
Leserinnlegg
Thorvaldsen, Gunnar og Holden, Lars. (2023).
The Development of Microhistorical Databases in Norway A Historiography.
Vis sammendrag
Norwegian work on microdata started out with the full count 1801 census and census and vital records from around the capital. Today, most census and ministerial records from 1801 until the mid-20th century have been scanned, transcriptions are being completed, much is encoded and made available via the websites of the Digital National Archives and UiT The Arctic University of Norway. This article complements a previous publication on empirical results from historical microdata. It is primarily organized by technical issues: digitization
of source materials, encoding and standardization, building of the Historical Population Register for the period since 1800, record linkage and source criticism as well as GIS. Presently, partner institutions are building the Historical Population Register with prolonged support from the Norwegian Research Council. This will contain longitudinal records of the nine million persons who lived in Norway since 1800. The register increasingly makes it possible to follow the entire population. Unique personal IDs with corresponding URLs to the person page providing links to many sources introduce a new level of historical documentation. Cross-sectional and vital records are being interlinked with automatic and manual record linkage software. Longitudinal data is available for searching as timelines and in Intermediate Data Structure format from UiT The Arctic University and for searching at Histreg.no, which also caters for manual editing. We are well on the way to creating a database that can fill the void in the two centuries before the Central Population Register starts in 1964.
Lund, Eiliv; Busund, Lill-Tove Rasmussen og Holden, Lars. (2023).
The curvilinear relationships between grand parity and incidence of hormone-dependent cancers; follow-up of postmenopausal women in the Norwegian 1960 Census.
Vis sammendrag
Breast, ovarian and endometrial cancers are named hormone dependent cancers (HDC) because of the effects of endogenous hormones, including parity, on the incidence rates. Here, we will test the hypothesis that each additional child has the same relative preventive effect on the risk of each of the three cancer sites and with similar shapes of the incidence curves over the extended exposure range, 1 - 18 children in postmenopausal women.
The study is based on parity information from the Norwegian 1960 Census for women aged 45-89 years. A total of 385 816 married women answered the question of number of children in present marriage to a civil servant. Follow-up continued until the first of any of the HDC diagnosis, death, or end of follow-up 2005 through linkages based on the unique Norwegian birth number. Included were 16 905 breast cancers, 3 827 ovarian cancers and 3 834 endometrial cancers. Based on person-years (PY), the percentage change in incidence rates of the three cancer sites for each additional child was calculated using a logit regression model including models with higher order terms. A new statistical method for analyses of collinearity between parity and age at first birth has been developed. Age at marriage was used as a proxy for age at first birth.
Parity had strong linear effects on the incidence rates for all three cancer sites (p<2e-16). The percentage decrease for each of the cancer diagnosis for an additional child were for breast cancer 10.5% (95% CI; 9.6-11.4), ovarian cancer 13.2% (11.2-15.3) and endometrial cancer 10.9% (8.9-12.8) with similar curvilinear relationship. Models with higher order terms gave slightly better fit to the data with a stronger protective effect for increasing parity on ovarian cancers, while for breast cancer age became more important. Combining the incidence of all three cancers gave a percentage decrease for each additional child of 11.0% (10.1-11.8). The risk for HDC cancer was reduced with earlier age at marriage (first birth) for women with 1-2 children for breast cancer and ovarian cancer and 1 child for endometrial cancer, but the effect was smaller than one additional child. Age of the women at marriage was not significant for the sum of the three cancers.
The study demonstrated the strong, regular protective effect of each additional child or full-term pregnancy on the incidence rates of the hormone-dependent cancers throughout the exposure range and with similar curvilinear relations. Reduced fertility is a common, strong etiological factor for the three hormone-dependent cancers in postmenopausal women. These findings support a hypothesis that similar immunological changes during each pregnancy could be the biological explanation.
Hjort, Maria Astrup; Solbakken, Synne; Reinertsen, Hilde; Jendal, Håkon; Rana, Shahzad; Andresen, Herbjørn; Holden, Lars og Bokhari, Laila. (2023).
Rapport. Utvalget for bevaring av digitalt skapt dokumentasjon. 15. mai 2023.
NVA
Rapport
Vis sammendrag
Digitalisering har utfordret Arkivverkets arbeid og rolle, og vil de neste tiårene fortsette å utfordre. Hele arkivsektoren opplever et behov for tydeligere retning og retningslinjer for å ta avgjørelser om hva som skal bevares og kasseres av digitalt skapt dokumentasjon. Det digitale formatet utløser en rekke problemstillinger knyttet til blant annet omfanget av bevaring, ressursbruk, digitale løsninger og personvern. Ny arkivlov og -forskrift er under utarbeidelse, men det er også behov for grundigere drøfting av spørsmålet om bevaring av digitalt skapt dokumentasjon. Arkivverket oppnevnte derfor et utvalg som skal undersøke nettopp dette temaet, og komme med anbefalinger i det videre arbeidet. Denne rapporten er utvalgets svar på Arkivverkets bestilling.
Skoie, Mathilde; Holden, Lars; Røeggen, Vidar; Bakke, Pål; Wenaas, Lars; Løvhaug, Johannes Waage; Qvenild, Marte og Karlsen, Espen Sandøe. (2023).
Strategi for vitenskapelig publisering etter 2024.
Vis sammendrag
Visjon: I et ønsket framtidig publiseringslandskap har alle forskere lik tilgang til å lese og publisere. Alle vitenskapelige resultater deles åpent og uten forsinkelse gjennom seriøse publiseringskanaler som også er tilgjengelige for næringslivet, interesseorganisasjoner og allmenheten. Publiseringskanaler og publiseringstjenester er av høy kvalitet og sikrer umiddelbar åpen tilgang til forskningen og med rimelige kostnader som svarer til tjenestene utgiver leverer. Høy kvalitet innebærer faglige solide vurderinger og tilbakemeldinger og at publiseringskanalens rutiner samsvarer med faglige standarder for å akseptere publisering av forskningsresultater, at forskningsintegritet ivaretas og at publiseringsprosessene er effektive og ivaretar fullføringen av forskningen på en god måte. Vi ønsker et mangfold av publiseringskanaler som er under forskersamfunnenes kontroll.
Med mandat fra Langtidsplanen for forskning og høyere utdanning 2023 – 2032 (LTP) ble det nedsatt en arbeidsgruppe bestående av medlemmer fra Forskningsinstituttenes fellesarena (FFA), Universitets- og høgskolerådet (UHR), de Regionale Helseforetakene (RHF), Sikt, Direktoratet for høyere utdanning og kompetanse (HK-dir) og Forskningsrådet (også sekretariat).
Arbeidsgruppen fikk i oppdrag å bistå forskningsinstitusjonene med en strategi for norsk vitenskapelig publisering etter 2024. Bakgrunnen var et initiativ fra FFA og UHR, som ønsket dialog med myndighetene om hva de nasjonale mål og retningslinjer for åpen tilgang til vitenskapelige artikler ville innebære etter 2024, tidspunktet regjeringen har målfestet at all offentlig finansiert forskning skal være åpen tilgjengelig.
Resultatet av arbeidet presenteres i denne rapporten med tilhørende anbefalinger.
Holden, Lars; Løland, Anders og Kvaløy, Jan Terje. (2022).
Data misuse – or seven ways to fail with statistics.
NVA
Intervju
nrk, Dagsnytt atten; Holden, Lars; Stølen, Svein og Moe, Ola Borten. (2022).
Krisen i Forskningsrådet.
NVA
Programdeltagelse
Holden, Lars. (2022).
Akademisk frihet er i stor grad avklart for forskningsinstitutter.
NVA
Leserinnlegg
Holden, Lars. (2022).
Hvis vi gjør ytringsfrihet til et hovedproblem, kan det bli en avsporing i forhold til de store oppgavene til instituttene.
NVA
Leserinnlegg
Eiliv, Lund; Holden, Marit; Igor, Snapkov; Rasmussen, Busund Lill-Tove; Nikita, Shvetsov og Holden, Lars. (2022).
Trajectories of gene expression, seasonal influenza, and within-host seasonal immunity: transfer value to covid-19.
Olsen, Karina Standahl; Holden, Marit; Thalabard, Jean-Christophe; Busund, Lill-Tove Rasmussen; Lund, Eiliv og Holden, Lars. (2021).
Global blood gene expression profiles following a breast cancer diagnosis—Clinical follow-up in the NOWAC post-genome cohort.
Vis sammendrag
Objective
This explorative study aimed to assess if there are any time-dependent blood gene expression changes during the first one to eight years after breast cancer diagnosis, which can be linked to the clinical outcome of the disease.
Material and methods
A random distribution of follow-up time from breast cancer diagnosis till blood sampling was obtained by a nested, matched case-control design in the Norwegian Women and Cancer Post-genome Cohort. From 2002–5, women were invited to donate blood samples, regardless of any cancer diagnosis. At end of the study period in 2015, any cancer diagnoses in the 50 000 participants were obtained via linkage to the Norwegian Cancer Registry. For each breast cancer patient (n = 415), an age- and storage time-matched control was drawn. The design gave a uniform, random length of follow-up time, independent of cancer stage. Differences in blood gene expression between breast cancer cases and controls were identified using the Bioconductor R-package limma, using a moving window in time, to handle the varying time elapsed from diagnosis to blood sample.
Results
The number of differentially expressed genes between cases and controls were close to 2,000 in the first year after diagnosis, but fell sharply the second year. During the next years, a transient second increase was observed, but only in women with metastatic disease who later died, both compared to invasive cases that survived (p<0,001) and to metastatic cases that survived (p = 0.024). Among the differentially expressed genes there was an overrepresentation of heme metabolism and T cell-related processes.
Conclusion
This explorative analysis identified changing trajectories in the years after diagnosis, depending on clinical stage. Hypothetically, this could represent the escape of the metastatic cancer from the immune system.
Eikvil, Line; Holden, Marit; Holden, Lars og Brautaset, Olav. (2021).
Machine learning for screening mammography.
NVA
Rapport
Holden, Lars og Holden, Steinar. (2021).
Oljefondet kan styres med lavere kostnader enn i dag.
NVA
Leserinnlegg
Holden, Lars. (2021).
Velkommen til FFAs årskonferanse 2021. Forskningsinstituttenes fellesarena
NVA
Faglig foredrag
Søreide, Øystein; Olsen, Dag Rune; Lind, Guro Elisabeth og Holden, Lars. (2020).
Ingen forskning, ingen omstilling.
NVA
Leserinnlegg
Holden, Marit og Holden, Lars. (2020).
Statistics of Sparsely Sampled Curves.
Vis sammendrag
We develop new statistical methods for analyzing sparsely sampled curves that vary in time. The typical dataset is differences in log gene expressions from case-control pairs for a large number of genes sampled relative to time of diagnosis. We focus on weak signals in the gene expression in many genes instead of strong signals in a few genes. The methods are based on moving windows in time, hypothesis testing, dimension reductions and randomization of the time to observation.
Lund, Eiliv; Holden, Marit; Thalabard, Jean-Christophe; Busund, Lill-Tove Rasmussen; Snapkov, Igor og Holden, Lars. (2020).
Signals of Death - Post-Diagnostic Single Gene Expression Trajectories in Breast Cancer - A Proof of Concept.
Vis sammendrag
Using the time-dependent dynamics of gene expression from immune cells in blood, we aimed to explore single gene expression trajectories as biomarkers for death after a diagnosis of breast cancer introducing a new statistical method denoted Difference in Time Development Statistics (DTDS). This shows as proof of principle that the gene expression profiles from immune cells in blood differed in the postdiagnostic period are dependent on later vital status.
Holden, Lars; Boudko, Svetlana og Thorvaldsen, Gunnar. (2020).
Lenking og kobling i Historisk befolkningsregister.
Vis sammendrag
Historisk befolkningsregister, HBR, er et register over den norske befolkningen fra 1801 frem til Det sentrale folkeregisteret fra 1964. Det lages ved å lenke sammen personforekomster av samme person i folketellinger og kirkebøker og koble sammen nære familiemedlemmer.
Vi viser hvordan algoritmer brukes til å finne lenker og koblinger. Vi har funnet familierelasjoner i alle de nominative folketellingene, også der familiestilling ikke er beskrevet i folketellingen. Alle algoritmene baserer seg på likhet i navn, fødselsår, fødested, yrke, bosted og tilsvarende egenskaper hos familiemedlemmer. I tillegg sjekker vi at alle hendelsene gir et naturlig livsløp. Algoritmene må tilpasses de ulike kildene for å holde feilraten under en teoretisk målsetning på 1 % – noen fasit fins imidlertid ikke. Vi må for eksempel ha strengere kriterier for likhet i store kommuner som Oslo, enn i mindre kommuner og strengere i 1865-folketellingen enn i den mer nøyaktige 1891-folketellingen. Vi har funnet samme person i etterfølgende folketellinger på nasjonalt nivå ved å bruke sjeldne etternavn. Vi har også søkt etter lignende personforekomster i samme kommune og fylke i Digitalarkivet for alle personer i en av de nasjonale folketellingene.
Det er laget maskinelle lenker ved Registeringssentral for historiske data, UiT og Norsk Regnesentral. Ved nettstedet histreg.no er det også mulig å lage manuelle lenker. Vi viser utviklingen av bidragsytere, lenker og koblinger i databasen i den fireårige perioden til registeret.
Thorvaldsen, Gunnar; Sommerseth, Hilde Leikny og Holden, Lars. (2020).
Anvendelser av Norges historiske befolkningsregister.
Vis sammendrag
Norge har et sentralt landsdekkende folkeregister som ble startet opp i 1964, og for mange personer inneholder data som går lenger tilbake. For tida bygger vi et Historisk befolkningsregister (HBR) tilbake til 1801. Målet er å konstruere en nasjonal database for også å håndtere innenlandsk migrasjon, som er dårlig dekket i de nominative kildene til langt ut på 1900-tallet. HBR bygger primært på folketellingene og kirkebøkene i perioden, siden det har vært for arbeidskrevende å utnytte de kommunale folkeregistrene som ble ført for et økende antall steder til de ble landsdekkende etter krigen. For den åpne perioden fram til 1920-tallet er HBR tilgjengelig via tre nettbaserte grensesnitt. For det ene, par av lenkede folketellinger, hvor data om samme person på to ulike tidspunkt er sammenstilt, for det andre «Tidslinjer», der innførsler fra flere folketellinger og kirkebøker er lenket sammen, og histreg.no, der brukerne selv kan bidra i lenkingen basert på alle kildene i Digitalarkivet. Disse er godt egnet for genealogi og lokalhistoriske studier. HBR gjøres òg tilgjengelig som datafiler gjennom Intermediate Data Structure (IDS), som gir datagrunnlag for kvantitative studier. Denne artikkelen vil beskrive hovedpunkter i disse fire grensesnittene til det historiske befolkningsregistret, som er åpne for alle typer brukere.
Eikvil, Line; Holden, Marit; Holden, Lars og Brautaset, Olav. (2020).
Machine learning for screening mammography - Initial analyses on a first limited dataset.
NVA
Rapport
Holden, Lars. (2019).
Mixing of MCMC algorithms.
Vis sammendrag
We analyse MCMC chains focusing on how to find simulation parameters that give good mixing for discrete time, Harris ergodic Markov chains on a general state space X having invariant distribution π. The analysis uses an upper bound for the variance of the probability estimate. For each simulation parameter set, the bound is estimated from an MCMC chain using recurrence intervals. Recurrence intervals are a generalization of recurrence periods for discrete Markov chains. It is easy to compare the mixing properties for different simulation parameters. The paper gives general advice on how to improve the mixing of the MCMC chains and a new methodology for how to find an optimal acceptance rate for the Metropolis-Hastings algorithm. Several examples, both toy examples and large complex ones, illustrate how to apply the methodology in practice. We find that the optimal acceptance rate is smaller than the general recommendation in the literature in some of these examples.
Haugli, Håkon; Holden, Lars og Landstad, Agnes. (2019).
Underfinansiering bremser Norges kunnskapsmotor.
NVA
Leserinnlegg
Holden, Lars. (2019).
Instituttene ønsker å bli mer involvert i Forskningsrådets vurdering av forskerkompetanse.
NVA
Leserinnlegg
Olsen, Karina Standahl; Holden, Marit; Talabard, Jean-Christophe; Busund, Lill-Tove Rasmussen; Lund, Eiliv og Holden, Lars. (2019).
Post-diagnostic blood gene expression profiles in breast cancer - NOWAC Post-genome Cohort. Norsk forening for epidemiologi
NVA
poster
Salvatore, Stefania; Rand, Knut Dagestad; Grytten, Ivar; Ferkingstad, Egil; Domanska, Diana; Holden, Lars; Gheorghe, Marius; Mathelier, Anthony; Glad, Ingrid Kristine og Sandve, Geir Kjetil. (2019).
Beware the Jaccard: the choice of similarity measure is important and non-trivial in genomic colocalisation analysis.
Holden, Marit og Holden, Lars. (2019).
Parity and breast cancer
Gene expression in blood, normal and tumor tissue.
NVA
Rapport
Vasaasen, Erik; Holden, Lars og Løland, Anders. (2019).
Personopplysninger i forskningsprosjekter ved Norsk Regnesentral.
NVA
Rapport
Vis sammendrag
Hensikten med dette dokumentet er å dokumentere rutinene for behandling av sensitive personopplysninger i NRs forskningsprosjekter i tråd med NRs rutiner for internkontroll. Det sentrale formålet er å fastlegge hvem som er ansvarlig for hva når personopplysninger skal håndteres.
Dokumentet inneholder det som kreves etter Personopplysningsloven, med virkning fra 20.07.2018 som er tilpasset EØS-avtalen (forordning (EU) 2016/679) om vern av fysiske personer i forbindelse med behandling av personopplysninger og om fri utveksling av slike opplysninger (GDPR).
Lund, Eiliv; Holden, Marit og Holden, Lars. (2019).
BLOBREC – a blood-based test for breast cancer.
Vis sammendrag
BLOBREC is a test for distinguishing breast-cancer patients from population-based controls described by Dumeaux et al. Previously, we performed a quality control of the methods and procedures used for developing this test, and our analyses confirmed the results obtained by Dumeaux et al. The aim of these analyses were to study the properties of the BLOBREC test in the years before or after diagnosis, and compare with time of diagnosis. In addition, we looked at effects of parity in controls, and also used a clinical stress study. We had a case-control design with 539 pairs before diagnosis, 59 at and 429 after diagnosis. In the controls taken from the NOWAC postgenome biobank, we found no difference in percentage false positives (%P) between the pre- and postdiagnostic controls (37% and 34% respectively). The %P were similar to the casecontrol study at time of diagnosis; 37%. The %P for cases were except for one year before diagnosis similar to the controls pre- and postdiagnostic. Additionally, we found a weak, non-significant increase in %P for controls with many children. The stress data originated from the “second look” at one single centre in the national screening program for breast cancer. The %P (the per cent of positive tests) were lower both for cases and controls than for the original case-control series. These data were collected under more stringent conditions. Conclusion: the BLOBREC showed higher %P for cases at diagnosis than either before or after, while the %P for controls remained identical. As previous, the %P was higher for metastatic breast cancer. BLOBREC might be improved through a more stringent sampling of both cases and controls.
Holden, Lars og Fløtten, Tone. (2018).
Forskningsetikk for oppdragsforskning.
NVA
Rapport
Vis sammendrag
Med den nye forskningsetikkloven (Lov om organisering av forskningsetisk arbeid) har forskningsinstitusjonene fått et tydeligere og mer konkret ansvar for håndtering av forskningsetiske spørsmål. Institusjonene har nå et lovfestet ansvar for å sikre at de ansatte har relevant forskningsetisk kompetanse, og institusjonene skal ha rutiner for å behandle forskningsetiske saker. Den enkelte forsker har ansvar for å gjennom-føre sin forskning i samsvar med anerkjente vitenskapelige og forskningsetiske normer.
Eikvil, Line og Holden, Lars. (2018).
Bruk av Deep learning and Big Data i Mammografiprogrammet. Mammografiprogrammet
NVA
Faglig foredrag
Holden, Lars. (2018).
Historisk befolkningsregister og bioinformatikk. Bioinformatikk, Inst. for informatikk, Universitetet i Oslo
NVA
Faglig foredrag
Holden, Lars. (2018).
En instituttpolitikk som løser samfunnsutfordringer. Forskningsinstituttenes fellesarena, FFA
NVA
Faglig foredrag
Lund, Eiliv; Nakamura, Aurelie; Snapkov, Igor; Thalabard, Jean-Christophe; Olsen, Karina Standahl; Holden, Lars og Holden, Marit. (2018).
Each pregnancy linearly changes immune gene expression in the blood of healthy women compared with breast cancer patients.
Vis sammendrag
Background: There is a large body of evidence demonstrating long-lasting protective effect of each full-term pregnancy (FTP) on the development of breast cancer (BC) later in life, a phenomenon that could be related to both hormonal and immunological changes during pregnancies. In this work, we studied the pregnancy-associated differences in peripheral blood gene expression profiles between healthy women and women diagnosed with BC in a prospective design.
Methods: Using an integrated system epidemiology approach, we modeled BC incidence as a function of parity in the Norwegian Women and Cancer (NOWAC) cohort (165,000 women) and then tested the resulting mathematical model using gene expression profiles in blood in a nested case–control study (460 invasive case–control pairs) of women from the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis for immunological gene sets.
Results: A linear trend fitted the dataset precisely showing an 8% decrease in risk of BC for each FTP, independent of stratification on other risk factors and lasting for decades after a woman’s last FTP. Women with six children demonstrated 48% reduction in the incidence of BC compared to nulliparous. When we looked at gene expression, we found that 756 genes showed linear trends in cancer-free controls (false discovery rate [FDR] 5%), but this was not the case for any of the genes in BC cases. Gene set enrichment analysis of immunologic gene sets (C7 collection in Molecular Signatures Database) revealed 215 significantly enriched human gene sets (FDR 5%).
Conclusion: We found marked differences in gene expression and enrichment profiles of immunologic gene sets between BC cases and healthy controls, suggesting an important protective effect of the immune system on BC risk.
Sikorski, Krzysztof; Mehta, Adi; Inngjerdingen, Marit; Thakor, Flourina Kumar; Kling, Simon; Kalina, Tomas; Nyman, Tuula Anneli; Stensland, Maria; Zhou, Wei; Souza, Gustavo Antonio De; Holden, Lars; Stuchly, Jan; Templin, Markus og Lund-Johansen, Fridtjof. (2018).
A high-throughput pipeline for validation of antibodies.
Vis sammendrag
Western blotting (WB) is widely used to test antibody specificity, but the assay has low throughput and precision. Here we used preparative gel electrophoresis to develop a capture format for WB. Fractions with soluble, size-separated proteins facilitated parallel readout with antibody arrays, shotgun mass spectrometry (MS) and immunoprecipitation followed by MS (IP-MS). This pipeline provided the means for large-scale implementation of antibody validation concepts proposed by an international working group on antibody validation (IWGAV).Western blotting (WB) is widely used to test antibody specificity, but the assay has low throughput and precision. Here we used preparative gel electrophoresis to develop a capture format for WB. Fractions with soluble, size-separated proteins facilitated parallel readout with antibody arrays, shotgun mass spectrometry (MS) and immunoprecipitation followed by MS (IP-MS). This pipeline provided the means for large-scale implementation of antibody validation concepts proposed by an international working group on antibody validation (IWGAV).
Holden, Lars og Boudko, Svetlana. (2018).
The Norwegian historic population register and migration.
Vis sammendrag
This article describes the development of the Norwegian Historical Population Register, which is the first open national register. In the period 1735–1964, 9.7 million people lived in Norway, and for them 37.5 million events (such as birth, death, or migration) have been recorded in sources. We link together as many events as possible for the same persons and families, but only include links that have a high probability of being correct. The linking is performed by automatic methods and crowdsourcing. A national population register is important for migration research. It allows us to reconstruct (stepwise) internal migration in Norway, frequently followed by international migration from Norway, as well as return migration to Norway. Many non-Norwegian sources also specify place of birth by country, and this makes it possible to identify individuals in Norwegian sources.
Holden, Marit og Holden, Lars. (2018).
Parity and breast cancer - Gene expression in blood, normal and tumor tissue.
NVA
Rapport
Vasaasen, Erik; Holden, Lars og Løland, Anders. (2017).
Personopplysninger i forskningsprosjekter ved Norsk Regnesentral.
NVA
Rapport
Holden, Lars; Jullum, Martin og Sandve, Geir Kjetil. (2017).
Statistical modeling of repertoire overlap in entire sampling spaces.
Vis sammendrag
We analyze the distribution of T-cell clonotypes in a compartment like blood based on samples. In particular, we study how the distribution of clonotype frequencies changes between different samples. We consider this as a sampling problem and formulate the problem as a generalization of the classical statistical problem of comparing samples from an urn. Due to the low sampling size compared to the number of different clonotypes in the entire sampling space, the classical methodology that works directly with clonotype frequencies in samples is not suited. We approach this challenge by representing other properties of the sample. Our re-representation allows for easy sampling model fitting and testing under natural model conditions. Although we here focus on the application on clonotypes, the new methodology generalizes seamlessly to other applications.
Simovski, Boris; Vodak, Daniel; Gundersen, Sveinung; Domanska, Diana Ewa; Azab, Abdulrahman; Holden, Lars; Holden, Marit; Grytten, Ivar; Rand, Knut Dagestad; Drabløs, Finn; Johansen, Morten; Ortiz, Antonio Carlos Mora; Lund-Andersen, Christin; Fromm, Bastian; Eskeland, Ragnhild; Gabrielsen, Odd Stokke; Ferkingstad, Egil; Nakken, Sigve; Bengtsen, Mads; Nederbragt, Alexander Johan; Thorarensen, Hildur Sif; Akse, Johannes Andreas; Glad, Ingrid Kristine; Hovig, Johannes Eivind og Sandve, Geir Kjetil. (2017).
GSuite HyperBrowser: integrative analysis of dataset collections across the genome and epigenome.
Vis sammendrag
Background: Recent large-scale undertakings such as ENCODE and Roadmap Epigenomics have generated experimental data mapped to the human reference genome (as genomic tracks) representing a variety of functional elements across a large number of cell types. Despite the high potential value of these publicly available data for a broad variety of investigations, little attention has been given to the analytical methodology necessary for their widespread utilisation. Findings: We here present a first principled treatment of the analysis of collections of genomic tracks. We have developed novel computational and statistical methodology to permit comparative and confirmatory analyses across multiple and disparate data sources. We delineate a set of generic questions that are useful across a broad range of investigations and discuss the implications of choosing different statistical measures and null models. Examples include contrasting analyses across different tissues or diseases. The methodology has been implemented in a comprehensive open-source software system, the GSuite HyperBrowser. To make the functionality accessible to biologists, and to facilitate reproducible analysis, we have also developed a web-based interface providing an expertly guided and customizable way of utilizing the methodology. With this system, many novel biological questions can flexibly be posed and rapidly answered. Conclusions: Through a combination of streamlined data acquisition, interoperable representation of dataset collections and customizable statistical analysis with guided setup and interpretation, the GSuite HyperBrowser represents a first comprehensive solution for integrative analysis of track collections across the genome and epigenome. The software is available at: https://hyperbrowser.uio.no
Holden, Marit; Holden, Lars; Olsen, Karina Standahl og Lund, Eiliv. (2017).
Local In Time Statistics for detecting weak gene expression signals in blood – illustrated for prediction of metastases in breast cancer in the NOWAC Post-genome Cohort.
Vis sammendrag
Background: Functional genomics in a processual analysis cover the time-dependent changes in transcriptomics and epigenetics before diagnosis of a disease, reflecting the changes in both life style and disease processes. The aim of this paper is to explore the dynamic, time-dependent mechanisms of the metastatic processes, using blood transcriptomics and including time in a continuous manner. For achieving this goal, we have developed new statistical methods based on statistics that are local in time.
Methods: The new statistical method, Local in Time Statistics (LITS), is based on calculating statistics in moving windows and randomization. The method has been tested for the analysis of a dataset that collectively provides information on the blood transcriptome up to 8 years before breast cancer diagnosis. The dataset from the Norwegian Women and Cancer (NOWAC) Post-genome Cohort consists of 467 case-control pairs matched on birth year and time of blood sampling. The data for a pair are the difference in log2 gene expression between the case and control. The stratified analyses are based on important biological differences like metastatic versus non-metastatic cancer, and the mode of cancer detection, ie, screening-detected cancers versus clinically detected cancers. The dataset was used for examining whether the gene expression profile varies between cases and controls, with time, or between cases with and without metastases.
Results: The null hypotheses of no differences between cases and controls, no time-dependent changes, and no differences between different strata were all rejected. For screening-detected cancers, the probability of correct prediction of metastasis status was best in year 1 before diagnosis compared to year 3 and 4 before diagnosis for clinically detected cancers. The predictor was not very sensitive to the number of genes included.
Conclusion: Using a new statistical method, LITS, we have demonstrated time-dependent changes of the blood transcriptome up to 8 years before breast cancer diagnosis.
Holden, Lars. (2017).
Instituttenes bidrag til å løse store samfunnsutfordringer - hvordan kan LTP bidra? Kunnskapsdepartementet
NVA
Faglig foredrag
Holden, Lars. (2017).
Instituttsektors rolle i ph.d.-utdanningen. Universitets- og høgskolerådet
NVA
Faglig foredrag
Holden, Lars. (2017).
Hvordan har vi lykkes? Erfaringer fra Norsk Regnesentral. Nordlandsforskning
NVA
Faglig foredrag
Holden, Lars. (2017).
Hvordan påvirker og forandrer digitaliseringen forskningen? Forskningsrådet, Divisjon for samfunn og helse
NVA
Faglig foredrag
Holden, Lars. (2017).
Historisk befolkningsregister, åpen del. Slekt og Data, Oslo og Akershus
NVA
Faglig foredrag
Holden, Lars. (2016).
Bruk av Forskningsrådets virkemidler for å nå høy kvalitet. Realfagsfakultetene
NVA
Faglig foredrag
Lund, Eiliv; Holden, Lars; Bøvelstad, Hege; Plancade, Sandra Caroline; Mode, Nicolle; Günther, Clara-Cecilie; Nuel, Gregory; Thalabard, Jean-Christophe og Holden, Marit. (2016).
A new statistical method for curve group analysis of longitudinal gene expression data illustrated for breast cancer in the NOWAC postgenome cohort as a proof of principle.
Vis sammendrag
Background
The understanding of changes in temporal processes related to human carcinogenesis is limited. One approach for prospective functional genomic studies is to compile trajectories of differential expression of genes, based on measurements from many case-control pairs. We propose a new statistical method that does not assume any parametric shape for the gene trajectories.
Methods
The trajectory of a gene is defined as the curve representing the changes in gene expression levels in the blood as a function of time to cancer diagnosis. In a nested case–control design it consists of differences in gene expression levels between cases and controls. Genes can be grouped into curve groups, each curve group corresponding to genes with a similar development over time. The proposed new statistical approach is based on a set of hypothesis testing that can determine whether or not there is development in gene expression levels over time, and whether this development varies among different strata. Curve group analysis may reveal significant differences in gene expression levels over time among the different strata considered. This new method was applied as a “proof of concept” to breast cancer in the Norwegian Women and Cancer (NOWAC) postgenome cohort, using blood samples collected prospectively that were specifically preserved for transcriptomic analyses (PAX tube). Cohort members diagnosed with invasive breast cancer through 2009 were identified through linkage to the Cancer Registry of Norway, and for each case a random control from the postgenome cohort was also selected, matched by birth year and time of blood sampling, to create a case-control pair. After exclusions, 441 case-control pairs were available for analyses, in which we considered strata of lymph node status at time of diagnosis and time of diagnosis with respect to breast cancer screening visits.
Results
The development of gene expression levels in the NOWAC postgenome cohort varied in the last years before breast cancer diagnosis, and this development differed by lymph node status and participation in the Norwegian Breast Cancer Screening Program. The differences among the investigated strata appeared larger in the year before breast cancer diagnosis compared to earlier years.
Conclusions
This approach shows good properties in term of statistical power and type 1 error under minimal assumptions. When applied to a real data set it was able to discriminate between groups of genes with non-linear similar patterns before diagnosis.
Holden, Marit og Holden, Lars. (2016).
Analysis of gene expression in blood before diagnosis of ovarian cancer - Different statistical methods.
Vis sammendrag
The analyses in this note are based on a dataset with gene expression in blood before diagnosis of ovarian cancer. The dataset consists of case‐control pairs that are matched on birth year and time of blood sampling, and the data for a pair is the log2 difference in gene expression between the case and control. For each case‐ control pair the gene expression is measured once before diagnosis. As the blood samples of the different case‐controls pairs are measured at different points in time before diagnosis, we have used the dataset for examining whether the gene expression profile varies with time. We have also used the dataset for examining whether the gene expression profile varies between cases and controls, or between cases with and without spread (metastases), and for predicting whether a case has ovarian cancer with or without spread. We have used and adapted a method based on hypothesis testing using randomization, that is able to identify small changes that are varying slowly in time and/or among strata, by using a large number of genes in each hypothesis test and predictor. Even though the signals in the data are weak, we concluded that the gene expression profile varies in time, between cases and controls and between cases with and without spread (metastases). The results indicated that there is an increasing variation in the gene expression profiles when approaching the time of diagnosis, while the gene expression profiles far from diagnosis are more stable. The dataset is quite small, with only 59 case‐control pairs with spread and 28 without spread that are distributed over a seven year period before diagnosis. We can therefore not draw any firm conclusion about whether the predictive power of the method used for predicting the metastasis status of the cases is sufficiently good (p‐value 0.28, Fisher’s test). The best predictive power was observed in a two‐year period around year 5 before diagnosis (p‐value 0.12, Fisher’s test).
Holden, Lars. (2016).
The two subset recurrent property of Markov chains.
Vis sammendrag
This paper proposes a new type of recurrence where we divide the Markov chains into intervals that start when the chain enters into a subset A, then sample another subset B far away from A and end when the chain again return to A. The length of these intervals have the same distribution and if A and B are far apart, almost independent of each other. A and B may be any subsets of the state space that are far apart of each other and such that the movement between the subsets is repeated several times in a long Markov chain. The expected length of the intervals is used in a function that describes the mixing properties of the chain and improves our understanding of Markov chains.
The paper proves a theorem that gives a bound on the variance of the estimate for π(A), the probability for A under the limiting density of the Markov chain. This may be used to find the length of the Markov chain that is needed to explore the state space sufficiently. It is shown that the length of the periods between each time A is entered by the Markov chain, has a heavy tailed distribution. This increases the upper bound for the variance of the estimate π(A).
The paper gives a general guideline on how to find the optimal scaling of parameters in the Metropolis-Hastings simulation algorithm that implicit determine the acceptance rate. We find examples where it is optimal to have a much smaller acceptance rate than what is generally recommended in the literature and also examples where the optimal acceptance rate vanishes in the limit.
Holden, Lars. (2016).
Forskning og innovasjon for omstilling - instituttenes bidrag. NHO
NVA
Faglig foredrag
Olsen, Karina Standahl; Holden, Lars; Bøvelstad, Hege; Plancade, Sandra; Günther, Clara-Cecilie; Thalabard, Jean-Christophe; Holden, Marit og Lund, Eiliv. (2016).
Blood gene expression profiles reflect temporality and clinical parameters up to six years before breast cancer diagnosis – The Norwegian Women and Cancer Post-genome cohort (Kvinner og Kreft-studien). NTNU
NVA
poster
Holden, Lars. (2016).
Instituttene svarer på Langtidsplanen. Forskningsinstituttenes fellesarena
NVA
Faglig foredrag
Olsen, Karina Standahl; Holden, Lars; Bøvelstad, Hege; Plancade, Sandra; Günther, Clara-Cecilie; Thalabard, Jean-Christophe; Holden, Marit og Lund, Eiliv. (2016).
Blood gene expression profiles reflect temporality and clinical parameters up to six years before breast cancer diagnosis – The Norwegian. Norsk Forening for epidemiologi
NVA
poster
Holden, Marit og Holden, Lars. (2016).
Detecting weak gene expression signals in blood before diagnosis of cancer - Comparing breast, ovarian and lung cancer.
NVA
Rapport
Holden, Marit og Holden, Lars. (2016).
Statistical analysis of gene expression in blood before diagnosis of breast cancer.
Vis sammendrag
The analyses in this note are based on a dataset with gene expression in blood before diagnosis of breast cancer. The dataset consists of case‐control pairs that are matched on birth year and time of blood sampling, and the data for a pair is the log2 difference in gene expression between the case and control. For each case‐ control pair the gene expression is measured once before diagnosis. As the blood samples of the different case‐controls pairs are measured at different points in time before diagnosis, we have used the dataset for examining whether the gene expression profile varies with time. We have also used the dataset for examining whether the gene expression profile varies between cases and controls, or between cases with and without spread (metastases), and for predicting whether a case has breast cancer with or without spread. The dataset consists of two subdatasets, one where the cases participated in the screening program (the screening group) and one where for cases did not participate in the screening program (the clinical group). All analyses have been performed separately for these two subdatasets. We have used and adapted a method based on hypothesis testing using randomization, that is able to identify small changes that are varying slowly in time and/or among strata, by using a large number of genes in each hypothesis test and predictor. Even though the signals in the data are weak, we concluded that the gene expression profile varies in time, between cases and controls and between cases with and without spread (metastases). The dataset is quite small, with only 108 (30) case‐control pairs with spread and 272 (57) without spread in the screening (clinical) group, that are distributed over an eight year period before diagnosis. We can therefore not draw any firm conclusion about whether the predictive power of the method used for predicting the metastasis status of the cases is sufficiently good. In the screening group we obtained p‐value 0.5 for the entire period but 0.03 for the last year before diagnosis. For the clinical group the p‐value for the entire period was 0.05. Here the results indicated best prediction 3‐4 years before diagnosis. The p‐value is equal 0.05 in this time period but this may be due to a small data set).
Ferkingstad, Egil; Holden, Lars og Sandve, Geir Kjetil F.. (2015).
Monte Carlo Null Models for Genomic Data.
Holden, Lars og Boudko, Svetlana. (2015).
The Norwegian historic population register and migration.
Vis sammendrag
This paper describes the building of a Norwegian historical population register that is under construction. It is based on linking together person entries from a large number of sources by linking algorithms and crowd sourcing. There are 9.7 million residents of Norway in the period 1735 - 1964 and 37.5 million events in most relevant sources. We want to link together as many events as possible for the same persons and families but only include links that have a high probability to be correct.
As the first open national population register, we believe that it will be particular important for migration studies. It is much easier to follow both national and international migration on a national level. Quite many of the international migration sources are national, and place of birth is specified by nationality for persons born abroad.
Holden, Lars. (2015).
Internet based record linkage in the Historical Population Register. Universitetet i Stavanger
NVA
Vitenskapelig foredrag
Holden, Lars. (2015).
Fra (sfi)2 til Big Insight. Hva har vi lært og hva tar vi med oss videre. Norges forskningsråd
NVA
Faglig foredrag
Holden, Lars. (2015).
Classify strata.
Vis sammendrag
We assume there is a slight difference in the average value of the gene expression for a group of genes between two strata/time periods. There is no prior knowledge on which genes where the gene expression differs between the two strata. We test out the power of a large number of test statistics in order to identify whether the observed difference between the averages is significant. Secondly, we test out a large number of test statistics ability to classify new patients into the two strata based on the genes identified in the first analysis. This is performed both with data from one time-period and for cases where there is data from several time periods. Data from several time periods may be valuable if we expect a time development relative to time to diagnosis that is characteristic for the different strata.
Olsen, Dag Rune og Holden, Lars. (2015).
Samarbeid om fremragende og innovativ forskning.
NVA
Leserinnlegg
Holden, Marit; Günther, Clara-Cecilie og Holden, Lars. (2015).
Verification of a blood-based test for breast-cancer (BLOBREC) - Distinguishing breast-cancer patients from population-based controls.
Vis sammendrag
BLOBREC is a test for distinguishing breast‐cancer patients from population‐based controls described by Dumeaux et al. We have performed a quality control of the methods and procedures used for developing this test. Besides reproducing results obtained using exactly the same datasets as Dumeaux et al., we examined how sensitive the test results are to the approach selected when preprocessing the data, and whether the test results are influenced by drug use, smoking, or stress due to a potential cancer diagnosis. We also examined if the test results for the breast‐cancer patients depend on whether the patient participated in the screening program. A data et intended for examining the effect of stress was used as a validation dataset for the test. Our analyses confirm the results obtained by Dumeaux et al. We obtain comparable results when using different approaches for preprocessing the data. Prediction performance for the datasets used when developing the test is clearly better than for the validation dataset. Batch effects and other differences between the datasets are the most likely explanations for this difference. However, the validation dataset consists of many different subgroups of individuals with a limited number of individuals in each subgroup, making the interpretation uncertain. We were not able to show that the test is influenced by stress, drug use or smoking, but again, the datasets are too small to draw any firm conclusions.
Holden, Marit og Holden, Lars. (2015).
Blood-based diagnostic tests for breast cancer:Additional subgroup analyses of the BLOBREC test.
NVA
Rapport
Ferkingstad, Egil; Sandve, Geir Kjetil F. og Holden, Lars. (2015).
Monte Carlo null models for genomic data. Institutt for matematiske fag, NTNU
NVA
Vitenskapelig foredrag
Vis sammendrag
As increasingly complex hypothesis-testing scenarios are considered in many scientific fields, analytic derivation of null distributions is often out of reach. To the rescue comes Monte Carlo testing, which may appear deceptively simple: as long as you can sample test statistics under the null hypothesis, the p-value is just the proportion of sampled test statistics that exceed the observed test statistic. Sampling test statistics is often simple once you have a Monte Carlo null model for your data, and defining some form of randomization procedure is also, in many cases, relatively straight-forward. However, there may be several possible choices of a randomization null model for the data and no clear-cut criteria for choosing among them. Obviously, different null models may lead to very different p-values, and a very low p-value may thus occur due to the inadequacy of the chosen null model. It is preferable to use assumptions about the underlying random data generation process to guide selection of a null model. In many cases, we may order the null models by increasing preservation of the data characteristics, and we argue in this paper that this ordering in most cases gives increasing p-values, that is, lower significance. We denote this as the null complexity principle. The principle gives a better understanding of the different null models and may guide in the choice between the different models.