| 1. |
- Edfors, Fredrik, et al.
(author)
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Gene-specific correlation of RNA and protein levels in human cells and tissues
- 2016
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In: Molecular Systems Biology. - : EMBO. - 1744-4292 .- 1744-4292. ; 12:10
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Journal article (peer-reviewed)abstract
- An important issue for molecular biology is to establish whether transcript levels of a given gene can be used as proxies for the corresponding protein levels. Here, we have developed a targeted proteomics approach for a set of human non-secreted proteins based on parallel reaction monitoring to measure, at steady-state conditions, absolute protein copy numbers across human tissues and cell lines and compared these levels with the corresponding mRNA levels using transcriptomics. The study shows that the transcript and protein levels do not correlate well unless a gene-specific RNA-to-protein (RTP) conversion factor independent of the tissue type is introduced, thus significantly enhancing the predictability of protein copy numbers from RNA levels. The results show that the RTP ratio varies significantly with a few hundred copies per mRNA molecule for some genes to several hundred thousands of protein copies per mRNA molecule for others. In conclusion, our data suggest that transcriptome analysis can be used as a tool to predict the protein copy numbers per cell, thus forming an attractive link between the field of genomics and proteomics.
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| 2. |
- Hallström, Björn, et al.
(author)
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Lund Stroke Register: hospitalization pattern and yield of different screening methods for first-ever stroke
- 2007
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 115:1, s. 49-54
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Journal article (peer-reviewed)abstract
- Objectives To explore case ascertainment, hospitalization, characteristics of both hospitalized and non-hospitalized patients in a population-based group of stroke patients. Materials and methods One-year screening in Lund-Orup district for first-ever strokes using multiple prospective and retrospective methods. Results A total of 456 patients with first-ever stroke (n = 412 prospective screening methods, n = 17 primary care, n = 12 hospital registers, n = 10 death register, n = 2 autopsy registers, n = 3 other). Hospitalization proportion within 14 days was 84%. Patients sent home from emergency unit (n = 36) were often males (75%), had low 28-day case-fatality (0%), and less severe strokes (median National Institute of Health Stroke Scale score 2 vs 4 for all). Patients managed solely within primary care (n = 18) were elderly (median age 89 vs 77 years for all), resided in nursing homes (86% vs 8% for all) and had high 28-day-case-fatality (61%). Conclusions Hospitalization was lower than expected. Two main categories of patients were not hospitalized: elderly patients at nursing homes with high case-fatality and patients with mild stroke.
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| 3. |
- Lindgren, Arne, et al.
(author)
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Prevalence of Stroke and Vascular Risk Factors among First-Degree Relatives of Stroke Patients and Control Subjects.
- 2005
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In: Cerebrovascular Diseases. - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 20:5, s. 381-387
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Journal article (peer-reviewed)abstract
- <i>Background:</i> Genetic and environmental factors may be of importance for stroke risk. We assessed the prevalence of stroke and vascular risk factors among first-degree relatives and spouses of stroke patients and control subjects. <i>Methods:</i> As a part of the Lund Stroke Register study, we asked 925 consecutive patients with first-ever stroke and 286 control subjects to complete a questionnaire about all their first-degree relatives and spouses. The questionnaires addressed whether these relatives had been affected by stroke or TIA, hypertension, heart disease, diabetes mellitus, and if they were smokers. <i>Results:</i> A total of 606 patients and 261 control subjects returned the questionnaire, providing information on 4,972 first-degree relatives and 738 spouses. The prevalence of stroke or TIA was 12.3% among first-degree relatives of patients and 7.5% among first-degree relatives of control subjects (OR 1.74, 95% CI 1.36–2.22). Corresponding results for hypertension were 21.0 and 16.7% (OR 1.33, 95% CI 1.10–1.60). The prevalences of heart disease, diabetes mellitus and smoking did not differ significantly between first-degree relatives of patients and control subjects. Spouses of patients and control subjects had similar prevalences of stroke or TIA and vascular risk factors. <i>Conclusions:</i> The prevalences of stroke or TIA and hypertension are higher among first-degree relatives of stroke patients than among first-degree relatives of control subjects. This, and the lack of differences between spouses of patients and control subjects, indicates that an increased risk of stroke may in part be explained by heritability of hypertension.
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| 4. |
- Andersson, Sandra, et al.
(author)
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The Transcriptomic and Proteomic Landscapes of Bone Marrow and Secondary Lymphoid Tissues
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. e115911-
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Journal article (peer-reviewed)abstract
- Background: The sequencing of the human genome has opened doors for global gene expression profiling, and the immense amount of data will lay an important ground for future studies of normal and diseased tissues. The Human Protein Atlas project aims to systematically map the human gene and protein expression landscape in a multitude of normal healthy tissues as well as cancers, enabling the characterization of both housekeeping genes and genes that display a tissue-specific expression pattern. This article focuses on identifying and describing genes with an elevated expression in four lymphohematopoietic tissue types (bone marrow, lymph node, spleen and appendix), based on the Human Protein Atlas-strategy that combines high throughput transcriptomics with affinity-based proteomics. Results: An enriched or enhanced expression in one or more of the lymphohematopoietic tissues, compared to other tissue-types, was seen for 693 out of 20,050 genes, and the highest levels of expression were found in bone marrow for neutrophilic and erythrocytic genes. A majority of these genes were found to constitute well-characterized genes with known functions in lymphatic or hematopoietic cells, while others are not previously studied, as exemplified by C19ORF59. Conclusions: In this paper we present a strategy of combining next generation RNA-sequencing with in situ affinity-based proteomics in order to identify and describe new gene targets for further research on lymphatic or hematopoietic cells and tissues. The results constitute lists of genes with enriched or enhanced expression in the four lymphohematopoietic tissues, exemplified also on protein level with immunohistochemical images.
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| 5. |
- Anfelt, Josefine, et al.
(author)
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Using Transcriptomics To Improve Butanol Tolerance of Synechocystis sp Strain PCC 6803
- 2013
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In: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 79:23, s. 7419-7427
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Journal article (peer-reviewed)abstract
- Cyanobacteria are emerging as promising hosts for production of advanced biofuels such as n-butanol and alkanes. However, cyanobacteria suffer from the same product inhibition problems as those that plague other microbial biofuel hosts. High concentrations of butanol severely reduce growth, and even small amounts can negatively affect metabolic processes. An understanding of how cyanobacteria are affected by their biofuel product can enable identification of engineering strategies for improving their tolerance. Here we used transcriptome sequencing (RNA-Seq) to assess the transcriptome response of Synechocystis sp. strain PCC 6803 to two concentrations of exogenous n-butanol. Approximately 80 transcripts were differentially expressed at 40 mg/liter butanol, and 280 transcripts were different at 1 g/liter butanol. Our results suggest a compromised cell membrane, impaired photosynthetic electron transport, and reduced biosynthesis. Accumulation of intracellular reactive oxygen species (ROS) scaled with butanol concentration. Using the physiology and transcriptomics data, we selected several genes for overexpression in an attempt to improve butanol tolerance. We found that overexpression of several proteins, notably, the small heat shock protein HspA, improved tolerance to butanol. Transcriptomics-guided engineering created more solvent-tolerant cyanobacteria strains that could be the foundation for a more productive biofuel host.
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| 6. |
- Árnason, Úlfur, et al.
(author)
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The reversal of human phylogeny : Homo left Africa as erectus, came back as sapiens sapiens
- 2020
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In: Hereditas. - : Springer Science and Business Media LLC. - 0018-0661 .- 1601-5223. ; 157:1
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Research review (peer-reviewed)abstract
- Background: The molecular out of Africa hypothesis, OOAH, has been considered as an established fact amid population geneticists for some 25–30 years despite the early concern with it among phylogeneticists with experience beyond that of Homo. The palaeontological support for the hypothesis is also questionable, a circumstance that in the light of expanding Eurasian palaeontological knowledge has become accentuated through the last decades. Results: The direction of evolution in the phylogenetic tree of modern humans (Homo sapiens sapiens, Hss) was established inter alia by applying progressive phylogenetic analysis to an mtDNA sampling that included a Eurasian, Lund, and the African Mbuti, San and Yoruba. The examination identified the African populations as paraphyletic, thereby compromising the OOAH. The finding, which was consistent with the out of Eurasia hypothesis, OOEH, was corroborated by the mtDNA introgression from Hss into Hsnn (Neanderthals) that demonstrated the temporal and physical Eurasian coexistence of the two lineages. The results are consistent with the palaeontologically established presence of H. erectus in Eurasia, a Eurasian divergence between H. sapiens and H. antecessor ≈ 850,000 YBP, an Hs divergence between Hss and Hsn (Neanderthals + Denisovans) ≈ 800,000 YBP, an mtDNA introgression from Hss into Hsnn* ≈ 500,000 YBP and an Eurasian divergence among the ancestors of extant Hss ≈ 250,000 YBP at the exodus of Mbuti/San into Africa. Conclusions: The present study showed that Eurasia was not the receiver but the donor in Hss evolution. The findings that Homo left Africa as erectus and returned as sapiens sapiens constitute a change in the understanding of Hs evolution to one that conforms to the extensive Eurasian record of Hs palaeontology and archaeology.
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| 7. |
- Bergman, Julia, et al.
(author)
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The human adrenal gland proteome defined by transcriptomics and antibody-based profiling.
- 2017
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In: Endocrinology. - : Endocrine Society. - 0013-7227 .- 1945-7170. ; 158:2, s. 239-251
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Journal article (peer-reviewed)abstract
- The adrenal gland is a composite endocrine organ with vital functions that include the synthesis and release of glucocorticoids and catecholamines. To define the molecular landscape that underlies the specific functions of the adrenal gland, we combined a genome-wide transcriptomics approach using messenger RNA sequencing of human tissues with immunohistochemistry-based protein profiling on tissue microarrays. Approximately two-thirds of all putative protein coding genes were expressed in the adrenal gland, and the analysis identified 253 genes with an elevated pattern of expression in the adrenal gland, with only 37 genes showing a markedly greater expression level (more than fivefold) in the adrenal gland compared with 31 other normal human tissue types analyzed. The analyses allowed for an assessment of the relative expression levels for well-known proteins involved in adrenal gland function but also identified previously poorly characterized proteins in the adrenal cortex, such as the FERM (4.1 protein, ezrin, radixin, moesin) domain containing 5 and the nephroblastoma overexpressed (NOV) protein homolog. We have provided a global analysis of the adrenal gland transcriptome and proteome, with a comprehensive list of genes with elevated expression in the adrenal gland and spatial information with examples of protein expression patterns for corresponding proteins. These genes and proteins constitute important starting points for an improved understanding of the normal function and pathophysiology of the adrenal glands.
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| 8. |
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| 9. |
- Bidon, Tobias, et al.
(author)
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Brown and Polar Bear Y Chromosomes Reveal Extensive Male-Biased Gene Flow within Brother Lineages
- 2014
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 31:6, s. 1353-1363
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Journal article (peer-reviewed)abstract
- Brown and polar bears have become prominent examples in phylogeography, but previous phylogeographic studies relied largely on maternally inherited mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y chromosome, a natural counterpart to mtDNA, has remained underexplored. Although this paternally inherited chromosome is indispensable for comprehensive analyses of phylogeographic patterns, technical difficulties and low variability have hampered its application in most mammals. We developed 13 novel Y-chromosomal sequence and microsatellite markers from the polar bear genome and screened these in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390-kb-long Y-chromosomal scaffold using sequencing data from published male ursine genomes. Y chromosome evidence support the emerging understanding that brown and polar bears started to diverge no later than the Middle Pleistocene. Contrary to mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic sister (or rather brother) lineages, without signals of introgression, 2) male-biased gene flow across continents and on phylogeographic time scales, and 3) male dispersal that links the Alaskan ABC islands population to mainland brown bears. Due to female philopatry, mtDNA provides a highly structured estimate of population differentiation, while male-biased gene flow is a homogenizing force for nuclear genetic variation. Our findings highlight the importance of analyzing both maternally and paternally inherited loci for a comprehensive view of phylogeographic history, and that mtDNA-based phylogeographic studies of many mammals should be reevaluated. Recent advances in sequencing technology render the analysis of Y-chromosomal variation feasible, even in nonmodel organisms.
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| 10. |
- Butler, L. M., et al.
(author)
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Analysis of Body-wide Unfractionated Tissue Data to Identify a Core Human Endothelial Transcriptome
- 2016
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In: Cell Systems. - : Cell Press. - 2405-4712. ; 3:3, s. 287-301.e3
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Journal article (peer-reviewed)abstract
- Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds. The majority of identified transcripts could be detected in cultured endothelial cells from various vascular beds, and we observed maintenance of relative expression in early passage cells. In summary, we describe a widely applicable method to determine cell-type-specific transcriptome profiles in a whole-organism context, based on differential abundance across tissues. We identify potential vascular drug targets or endothelial biomarkers and highlight candidates for functional studies to increase understanding of the endothelium in health and disease.
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