The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform

Sissel Jentoft - One of the best experts on this subject based on the ideXlab platform.

  • Disentangling the immune response and host-pathogen interactions in Francisella noatunensis infected Atlantic Cod.
    Comparative biochemistry and physiology. Part D Genomics & proteomics, 2019
    Co-Authors: Monica H. Solbakken, Tone F. Gregers, Kjetill S. Jakobsen, Sissel Jentoft, Trond Reitan, Helene Mikkelsen, Oddmund Bakke, Marit Seppola
    Abstract:

    The genetic repertoire underlying teleost immunity has been shown to be highly variable. A rare example is Atlantic Cod and its relatives Gadiformes that lacks a hallmark of vertebrate immunity: Major Histocompatibility Complex class II. No immunological studies so far have fully unraveled the functionality of this particular immune system. Through global transcriptomic profiling, we investigate the immune response and host-pathogen interaction of Atlantic Cod infected with the facultative intracellular bacterium Francisella noatunensis. We find that Atlantic Cod displays an overall classic innate immune response with inflammation, acute-phase proteins and cell recruitment through up-regulation of e.g. IL1B, fibrinogen, cathelicidin, hepcidin and several chemotactic cytokines such as the neutrophil attractants CXCL1 and CXCL8. In terms of adaptive immunity, we observe up-regulation of interferon gamma followed by up-regulation of several MHCI transcripts and genes related to antigen transport and loading. Finally, we find up-regulation of immunoglobulins and down-regulation of T-cell and NK-like cell markers. Our analyses also uncover some contradictory transcriptional findings such as up-regulation of anti-inflammatory IL10 as well as down-regulation of the NADPH oxidase complex and myeloperoxidase. This we interpret as the result of host-pathogen interactions where F. noatunensis modulates the immune response. In summary, our results suggest that Atlantic Cod mounts a classic innate immune response as well as a neutrophil-driven response. In terms of adaptive immunity, both endogenous and exogenous antigens are being presented on MHCI and antibody production is likely enabled through direct B-cell stimulation with possible neutrophil help. Collectively, we have obtained novel insight in the orchestration of the Atlantic Cod immune system and determined likely targets of F. noatunensis host-pathogen interactions.

  • Trans-oceanic genomic divergence of Atlantic Cod ecotypes is associated with large inversions
    Heredity, 2017
    Co-Authors: Paul R. Berg, Ian Bradbury, Paul Bentzen, Sissel Jentoft, Jeffrey A. Hutchings, Bastiaan Star, Christophe Pampoulie, Kjetill S. Jakobsen
    Abstract:

    Chromosomal rearrangements such as inversions can play a crucial role in maintaining polymorphism underlying complex traits and contribute to the process of speciation. In Atlantic Cod (Gadus morhua), inversions of several megabases have been identified that dominate genomic differentiation between migratory and nonmigratory ecotypes in the Northeast Atlantic. Here, we show that the same genomic regions display elevated divergence and contribute to ecotype divergence in the Northwest Atlantic as well. The occurrence of these inversions on both sides of the Atlantic Ocean reveals a common evolutionary origin, predating the >100 000-year-old trans-Atlantic separation of Atlantic Cod. The long-term persistence of these inversions indicates that they are maintained by selection, possibly facilitated by coevolution of genes underlying complex traits. Our data suggest that migratory behaviour is derived from more stationary, ancestral ecotypes. Overall, we identify several large genomic regions-each containing hundreds of genes-likely involved in the maintenance of genomic divergence in Atlantic Cod on both sides of the Atlantic Ocean.

  • An improved genome assembly uncovers prolific tandem repeats in Atlantic Cod
    BMC genomics, 2017
    Co-Authors: Ole K. Tørresen, Sissel Jentoft, Bastiaan Star, William Brynildsen Reinar, Harald Grove, Jason R. Miller, Brian P. Walenz, James R. Knight, Jenny M. Ekholm, Paul Peluso
    Abstract:

    The first Atlantic Cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated for complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software now enable the generation of more contiguous genome assemblies. By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have created a substantially improved version of the Atlantic Cod genome assembly. The sequence contiguity of this assembly is increased fifty-fold and the proportion of gap-bases has been reduced fifteen-fold. Compared to other vertebrates, the assembly contains an unusual high density of tandem repeats (TRs). Indeed, retrospective analyses reveal that gaps in the first genome assembly were largely associated with these TRs. We show that 21% of the TRs across the assembly, 19% in the promoter regions and 12% in the Coding sequences are heterozygous in the sequenced individual. The inclusion of PacBio reads combined with the use of multiple assembly programs drastically improved the Atlantic Cod genome assembly by successfully resolving long TRs. The high frequency of heterozygous TRs within or in the vicinity of genes in the genome indicate a considerable standing genomic variation in Atlantic Cod populations, which is likely of evolutionary importance.

  • an improved genome assembly uncovers prolific tandem repeats in Atlantic Cod
    bioRxiv, 2016
    Co-Authors: Ole K. Tørresen, Sissel Jentoft, Bastiaan Star, William Brynildsen Reinar, Harald Grove, Jason R. Miller, Brian P. Walenz, James R. Knight, Jenny M. Ekholm, Paul Peluso
    Abstract:

    Background: The first Atlantic Cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated for complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software now enable the generation of more contiguous genome assemblies. Results: By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have created a substantially improved version of the Atlantic Cod genome assembly. The sequence contiguity of this assembly is increased fifty-fold and the proportion of gap-bases has been reduced fifteen-fold. Compared to other vertebrates, the assembly contains an unusual high density of tandem repeats (TRs). Indeed, retrospective analyses reveal that gaps in the first genome assembly were largely associated with these TRs. We show that 21 % of the TRs across the assembly, 19 % in the promoter regions and 12 % in the Coding sequences are heterozygous in the sequenced individual. Conclusions: The inclusion of PacBio reads combined with the use of multiple assembly programs drastically improved the Atlantic Cod genome assembly by successfully resolving long TRs. The high frequency of heterozygous TRs within or in the vicinity of genes in the genome indicate a considerable standing genomic variation in Atlantic Cod populations, which is likely of evolutionary importance.

  • Genomic characterization of the Atlantic Cod sex-locus.
    Scientific reports, 2016
    Co-Authors: Bastiaan Star, Ole K. Tørresen, Alexander J. Nederbragt, Kjetill S. Jakobsen, Christophe Pampoulie, Sissel Jentoft
    Abstract:

    A variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic Cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic Cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on five different linkage groups (LG) in the genome. The largest of these regions, an approximately 55 Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY system. Genotypes in this region can be used genetically determine sex, whereas those in the other regions are inconsistently sex-linked. The identified region on LG11 and its surrounding genes have no clear sequence homology with genes or regulatory elements associated with sex-determination or differentiation in other species. The functionality of this sex-locus therefore remains unknown. The WGS strategy used here proved adequate for detecting the small regions associated with sex in this species. Our results highlight the evolutionary flexibility in genomic architecture underlying teleost sex-determination and allow practical applications to genetically sex Atlantic Cod.

Robert Fairweather - One of the best experts on this subject based on the ideXlab platform.

  • Range‐wide genomic data synthesis reveals transAtlantic vicariance and secondary contact in Atlantic Cod
    Ecology and Evolution, 2018
    Co-Authors: Robert Fairweather, Jakob Hemmer-hansen, Sarah J Helyar, Ian Bradbury, Mark De Bruyn, Paul Bentzen, Nina Overgaard Therkildsen, Gary R. Carvalho
    Abstract:

    Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic Cod (Gadus morhua), existing range-wide examinations suggest significant transAtlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transAtlantic phylogeography in Atlantic Cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transAtlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transAtlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic Cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.

  • range wide genomic data synthesis reveals transAtlantic vicariance and secondary contact in Atlantic Cod
    Ecology and Evolution, 2018
    Co-Authors: Robert Fairweather, Sarah J Helyar, Ian Bradbury, Mark De Bruyn, Paul Bentzen, Nina Overgaard Therkildsen, Jakob Hemmerhansen, Gary R. Carvalho
    Abstract:

    : Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic Cod (Gadus morhua), existing range-wide examinations suggest significant transAtlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transAtlantic phylogeography in Atlantic Cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transAtlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transAtlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic Cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.

Gary R. Carvalho - One of the best experts on this subject based on the ideXlab platform.

  • Range‐wide genomic data synthesis reveals transAtlantic vicariance and secondary contact in Atlantic Cod
    Ecology and Evolution, 2018
    Co-Authors: Robert Fairweather, Jakob Hemmer-hansen, Sarah J Helyar, Ian Bradbury, Mark De Bruyn, Paul Bentzen, Nina Overgaard Therkildsen, Gary R. Carvalho
    Abstract:

    Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic Cod (Gadus morhua), existing range-wide examinations suggest significant transAtlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transAtlantic phylogeography in Atlantic Cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transAtlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transAtlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic Cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.

  • range wide genomic data synthesis reveals transAtlantic vicariance and secondary contact in Atlantic Cod
    Ecology and Evolution, 2018
    Co-Authors: Robert Fairweather, Sarah J Helyar, Ian Bradbury, Mark De Bruyn, Paul Bentzen, Nina Overgaard Therkildsen, Jakob Hemmerhansen, Gary R. Carvalho
    Abstract:

    : Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic Cod (Gadus morhua), existing range-wide examinations suggest significant transAtlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transAtlantic phylogeography in Atlantic Cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transAtlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transAtlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic Cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.

Bastiaan Star - One of the best experts on this subject based on the ideXlab platform.

  • Trans-oceanic genomic divergence of Atlantic Cod ecotypes is associated with large inversions
    Heredity, 2017
    Co-Authors: Paul R. Berg, Ian Bradbury, Paul Bentzen, Sissel Jentoft, Jeffrey A. Hutchings, Bastiaan Star, Christophe Pampoulie, Kjetill S. Jakobsen
    Abstract:

    Chromosomal rearrangements such as inversions can play a crucial role in maintaining polymorphism underlying complex traits and contribute to the process of speciation. In Atlantic Cod (Gadus morhua), inversions of several megabases have been identified that dominate genomic differentiation between migratory and nonmigratory ecotypes in the Northeast Atlantic. Here, we show that the same genomic regions display elevated divergence and contribute to ecotype divergence in the Northwest Atlantic as well. The occurrence of these inversions on both sides of the Atlantic Ocean reveals a common evolutionary origin, predating the >100 000-year-old trans-Atlantic separation of Atlantic Cod. The long-term persistence of these inversions indicates that they are maintained by selection, possibly facilitated by coevolution of genes underlying complex traits. Our data suggest that migratory behaviour is derived from more stationary, ancestral ecotypes. Overall, we identify several large genomic regions-each containing hundreds of genes-likely involved in the maintenance of genomic divergence in Atlantic Cod on both sides of the Atlantic Ocean.

  • An improved genome assembly uncovers prolific tandem repeats in Atlantic Cod
    BMC genomics, 2017
    Co-Authors: Ole K. Tørresen, Sissel Jentoft, Bastiaan Star, William Brynildsen Reinar, Harald Grove, Jason R. Miller, Brian P. Walenz, James R. Knight, Jenny M. Ekholm, Paul Peluso
    Abstract:

    The first Atlantic Cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated for complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software now enable the generation of more contiguous genome assemblies. By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have created a substantially improved version of the Atlantic Cod genome assembly. The sequence contiguity of this assembly is increased fifty-fold and the proportion of gap-bases has been reduced fifteen-fold. Compared to other vertebrates, the assembly contains an unusual high density of tandem repeats (TRs). Indeed, retrospective analyses reveal that gaps in the first genome assembly were largely associated with these TRs. We show that 21% of the TRs across the assembly, 19% in the promoter regions and 12% in the Coding sequences are heterozygous in the sequenced individual. The inclusion of PacBio reads combined with the use of multiple assembly programs drastically improved the Atlantic Cod genome assembly by successfully resolving long TRs. The high frequency of heterozygous TRs within or in the vicinity of genes in the genome indicate a considerable standing genomic variation in Atlantic Cod populations, which is likely of evolutionary importance.

  • an improved genome assembly uncovers prolific tandem repeats in Atlantic Cod
    bioRxiv, 2016
    Co-Authors: Ole K. Tørresen, Sissel Jentoft, Bastiaan Star, William Brynildsen Reinar, Harald Grove, Jason R. Miller, Brian P. Walenz, James R. Knight, Jenny M. Ekholm, Paul Peluso
    Abstract:

    Background: The first Atlantic Cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated for complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software now enable the generation of more contiguous genome assemblies. Results: By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have created a substantially improved version of the Atlantic Cod genome assembly. The sequence contiguity of this assembly is increased fifty-fold and the proportion of gap-bases has been reduced fifteen-fold. Compared to other vertebrates, the assembly contains an unusual high density of tandem repeats (TRs). Indeed, retrospective analyses reveal that gaps in the first genome assembly were largely associated with these TRs. We show that 21 % of the TRs across the assembly, 19 % in the promoter regions and 12 % in the Coding sequences are heterozygous in the sequenced individual. Conclusions: The inclusion of PacBio reads combined with the use of multiple assembly programs drastically improved the Atlantic Cod genome assembly by successfully resolving long TRs. The high frequency of heterozygous TRs within or in the vicinity of genes in the genome indicate a considerable standing genomic variation in Atlantic Cod populations, which is likely of evolutionary importance.

  • Genomic characterization of the Atlantic Cod sex-locus.
    Scientific reports, 2016
    Co-Authors: Bastiaan Star, Ole K. Tørresen, Alexander J. Nederbragt, Kjetill S. Jakobsen, Christophe Pampoulie, Sissel Jentoft
    Abstract:

    A variety of sex determination mechanisms can be observed in evolutionary divergent teleosts. Sex determination is genetic in Atlantic Cod (Gadus morhua), however the genomic location or size of its sex-locus is unknown. Here, we characterize the sex-locus of Atlantic Cod using whole genome sequence (WGS) data of 227 wild-caught specimens. Analyzing more than 55 million polymorphic loci, we identify 166 loci that are associated with sex. These loci are located in six distinct regions on five different linkage groups (LG) in the genome. The largest of these regions, an approximately 55 Kb region on LG11, contains the majority of genotypes that segregate closely according to a XX-XY system. Genotypes in this region can be used genetically determine sex, whereas those in the other regions are inconsistently sex-linked. The identified region on LG11 and its surrounding genes have no clear sequence homology with genes or regulatory elements associated with sex-determination or differentiation in other species. The functionality of this sex-locus therefore remains unknown. The WGS strategy used here proved adequate for detecting the small regions associated with sex in this species. Our results highlight the evolutionary flexibility in genomic architecture underlying teleost sex-determination and allow practical applications to genetically sex Atlantic Cod.

  • An improved genome assembly uncovers a prolific tandem repeat structure in Atlantic Cod
    2016
    Co-Authors: Ole K. Tørresen, Sissel Jentoft, Bastiaan Star, William Brynildsen Reinar, Harald Grove, Jason R. Miller, Brian P. Walenz, James R. Knight, Jenny M. Ekholm, Paul Peluso
    Abstract:

    Background: The first Atlantic Cod (Gadus morhua) genome assembly published in 2011 was one of the early genome assemblies exclusively based on high-throughput 454 pyrosequencing. Since then, rapid advances in sequencing technologies have led to a multitude of assemblies generated from complex genomes, although many of these are of a fragmented nature with a significant fraction of bases in gaps. The development of long-read sequencing and improved software enable the generation of more contiguous genome assemblies. Results: By combining data from Illumina, 454 and the longer PacBio sequencing technologies, as well as integrating the results of multiple assembly programs, we have created a substantially improved version of the Atlantic Cod genome assembly. The sequence contiguity of this assembly has increased fifty-fold and the proportion of gap-bases has been reduced 15-fold. Compared to other vertebrates, the assembly contains an unusual high density of tandem repeats (TRs). Indeed, retrospective analyses reveal that gaps in the first genome assembly were largely associated with these TRs. We show that 21 % of the TRs across the assembly, 19 % in the promoter regions and 12 % in the Coding sequences are heterozygous in the sequenced individual. Conclusions: The use of multiple assembly programs combined with inclusion of PacBio reads drastically improved the Atlantic Cod genome assembly by successfully resolving long TRs. The high frequency of heterozygous TRs within or in the vicinity of genes in the genome indicate a considerable standing genomic variation in Atlantic Cod populations, which likely is of evolutionary importance.

Mark De Bruyn - One of the best experts on this subject based on the ideXlab platform.

  • Range‐wide genomic data synthesis reveals transAtlantic vicariance and secondary contact in Atlantic Cod
    Ecology and Evolution, 2018
    Co-Authors: Robert Fairweather, Jakob Hemmer-hansen, Sarah J Helyar, Ian Bradbury, Mark De Bruyn, Paul Bentzen, Nina Overgaard Therkildsen, Gary R. Carvalho
    Abstract:

    Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic Cod (Gadus morhua), existing range-wide examinations suggest significant transAtlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transAtlantic phylogeography in Atlantic Cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transAtlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transAtlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic Cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.

  • range wide genomic data synthesis reveals transAtlantic vicariance and secondary contact in Atlantic Cod
    Ecology and Evolution, 2018
    Co-Authors: Robert Fairweather, Sarah J Helyar, Ian Bradbury, Mark De Bruyn, Paul Bentzen, Nina Overgaard Therkildsen, Jakob Hemmerhansen, Gary R. Carvalho
    Abstract:

    : Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic Cod (Gadus morhua), existing range-wide examinations suggest significant transAtlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transAtlantic phylogeography in Atlantic Cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transAtlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transAtlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic Cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.