scholarly journals Development and Characterization of a Fixed Repertoire of Blood Transcriptome Modules Based on Co-expression Patterns Across Immunological States

2019 ◽  
Author(s):  
Matthew C Altman ◽  
Darawan Rinchai ◽  
Nicole Baldwin ◽  
Mohammed Toufiq ◽  
Elizabeth Whalen ◽  
...  

SUMMARYAs the capacity for generating large scale data continues to grow the ability to extract meaningful biological knowledge from it remains a limitation. Here we describe the development of a new fixed repertoire of transcriptional modules. It is meant to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome profiling data. It is supported by customized resources, which include analysis workflows, fingerprint grid plots data visualizations, interactive web applications providing access to a vast number of module-specific functional profiling reports, reference transcriptional profiles and give users the ability to visualize of changes in transcript abundance across the modular repertoire at different granularity levels. A use case focusing on a set of six modules comprising interferon-inducible genes is also provided. Altogether we hope that this resource will also serve as a framework for improving over time our collective understanding of the immunobiology underlying blood transcriptome profiling data.

2020 ◽  
Author(s):  
Matthew Altman ◽  
Darawan Rinchai ◽  
Nicole Baldwin ◽  
Mohammed Toufiq ◽  
Elizabeth Whalen ◽  
...  

Abstract As the capacity for generating large scale data continues to grow the ability to extract meaningful biological knowledge from it remains a limitation. Here we describe the development of a new fixed repertoire of transcriptional modules. It is meant to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome profiling data. It is supported by customized resources, which include analysis workflows, fingerprint grid plots data visualizations, interactive web applications. These provide access to a vast number of module-specific functional profiling reports, reference transcriptional profiles, and give users the ability to visualize changes in transcript abundance across the modular repertoire at different granularity levels. A use case focusing on a set of six modules comprising interferon-inducible genes is also provided. Taken together, this well-characterized set of modules may be employed for the interpretation and benchmarking of blood transcriptome profiles obtained within and across patient cohorts.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Matthew C. Altman ◽  
Darawan Rinchai ◽  
Nicole Baldwin ◽  
Mohammed Toufiq ◽  
Elizabeth Whalen ◽  
...  

AbstractAs the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via: https://drinchai.shinyapps.io/BloodGen3Module/.


2020 ◽  
Author(s):  
Hengyou Zhang ◽  
Zhenbin Hu ◽  
Yuming Yang ◽  
Xiaoqian Liu ◽  
Haiyan Lv ◽  
...  

Abstract Background: Seeds are the economic basis of oilseed crops, especially for soybean, thus far the most widely cultivated oilseed crop worldwide. Seed development is accompanied with a multitude of diverse cellular processes and revealing the underlying regulatory activities is critical for seed improvement. Results: Here, we profiled transcriptomes of developing seeds (20, 25, 30, 40 days after flowering) representing key points of seed development from early to full development. We identified a set of highly-abundant genes and highlighted the importance of these genes to support nutrient accumulation and transcriptional regulation in developing seeds. We identified 8,925 differentially expressed genes that exhibited temporal expression patterns over the course and had expression specificities in distinct tissues including seeds and non-seed tissues (roots, stems, leaves). Genes with specificities to non-seed tissues have tissue-specialized roles while remain relatively low transcript abundance in developing seeds, exhibiting their supportive roles spatially for seed development. Co-expression network analysis identified several under-explored genes in soybean that bridge tissue-specific gene modules. Conclusions: Our study provides a global view of gene activities and biological processes critical for seed formation in soybean and prioritizes a set of genes for further study. The results shed insight into the mechanism controlling seed development and storage reserves.


2018 ◽  
Vol 45 (2) ◽  
pp. 203 ◽  
Author(s):  
Oleg Gorshkov ◽  
Natalia Mokshina ◽  
Nadezda Ibragimova ◽  
Marina Ageeva ◽  
Natalia Gogoleva ◽  
...  

Restoration of stem vertical position after plant inclination is a widely spread version of plant orientation in accordance with gravity vector direction. Gravitropic behaviour of flax plants involves the formation of curvature in stem region that has ceased elongation long in advance of stem inclination. The important participants of such behaviour are phloem fibres with constitutively formed tertiary cell wall (G-layer). We performed the large-scale transcriptome profiling of phloem fibres isolated from pulling and opposite sides of gravitropic curvature and compared with control plant fibres. Significant changes in transcript abundance take place for genes encoding proteins of several ion channels, transcription factors and other regulating elements. The largest number of upregulated genes belonged to the cell wall category; many of those were specifically upregulated in fibres of pulling stem side. The obtained data permit to suggest the mechanism of fibre participation in gravitropic reaction that involves the increase of turgor pressure and the rearrangements of cell wall structure in order to improve contractile properties, and to identify the regulatory elements that operate specifically in the fibres of the pulling stem side making gelatinous phloem fibres an important element of gravitropic response in herbaceous plants.


2020 ◽  
Author(s):  
Darawan Rinchai ◽  
Basirudeen Kabeer ◽  
Mohammed Toufiq ◽  
Zohreh Tatari-Calderone ◽  
Sara Deola ◽  
...  

Abstract Background: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. Methods: We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. Results: As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: immunological relevance, therapeutic development relevance and SARS biology relevance. Conclusion: Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.


2020 ◽  
Vol 11 ◽  
Author(s):  
Arun Rawat ◽  
Darawan Rinchai ◽  
Mohammed Toufiq ◽  
Alexandra K. Marr ◽  
Tomoshige Kino ◽  
...  

Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes in the blood. Although less relevant to the study of psoriasis pathogenesis, blood transcriptome profiles can be readily compared across various diseases. Here, we used a pre-established set of 382 transcriptional modules as a common framework to compare changes in blood transcript abundance in two independent public psoriasis datasets. We then compared the resulting “transcriptional fingerprints” to those obtained for a reference set of 16 pathological or physiological states. The perturbations in blood transcript abundance in psoriasis were relatively subtle compared to the changes we observed in other autoimmune and auto-inflammatory diseases. However, we did observe a consistent pattern of changes for a set of modules associated with neutrophil activation and inflammation; interestingly, this pattern resembled that observed in patients with Kawasaki disease. This similarity between the blood-transcriptome signatures in psoriasis and Kawasaki disease suggests that the immune mechanisms driving their pathogenesis might be partially shared.


2020 ◽  
Vol 29 (4) ◽  
Author(s):  
Kisun Pokharel ◽  
Jaana Peippo ◽  
Meng-Hua Li ◽  
Juha Kantanen

Carefully coordinated interaction between the endometrium and embryo is critical for the establishment and maintenance of pregnancy in mammals. By exploring the gene expression dynamics of this tissue during preimplantation development, we may be able to get insight into the genetic mechanisms of reproduction during early pregnancy. Here, we have performed comparative transcriptome profiling of the endometrium in response to spherical (Day 7 to Day 12) and elongated (Day 13 to Day 17) embryos in Finnsheep, Texel and their F1 crosses using RNA sequencing (RNA-seq) approach. A total of 21125 genes were expressed in our dataset of which 554 were significantly (absolute log2 fold change > 2.5; adjusted p-value < 0.01) upregulated in the endometrium with elongated embryos. Highly abundant autosomal genes in the endometrium were associated with biological processes such as facilitation of maternal recognition of pregnancy, trophoblast elongation and implantation (LGALS15, CST3, CST6, and EEF1A1). Several endogenous retroviruses (ERVs) including a novel ERV gene located in a reduced FecL locus potentially associated with sheep prolificacy were expressed in our dataset. Comparative transcriptome profiling of the endometrium having spherical and elongated embryos revealed distinct gene expression patterns. Genes that were upregulated in response to elongated embryos indicated the importance of immune system at the maternal-embryo interface prior to implantation.


Author(s):  
Arun Rawat ◽  
Darawan Rinchai ◽  
Mohammed Toufiq ◽  
Alexandra Marr ◽  
Tomoshige Kino ◽  
...  

ABSTRACTBackgroundTranscriptome profiling approaches have been widely used in the investigation of mechanisms underlying psoriasis pathogenesis. In most instances, changes in transcript abundance have been measured in skin biopsies. Fewer studies have examined changes in the blood samples from patients with psoriasis. While changes in the periphery may be less relevant, the blood cell transcriptome analysis presents the distinct advantage of being amenable to comparison across diseases.MethodsTwo public psoriasis blood transcriptome datasets were reanalyzed and compared against reference datasets encompassing 16 immune states and pathologies, employing a recently established modular repertoire framework.ResultsAlthough perturbations in psoriasis were relatively subtle in comparison to other auto-immune or auto-inflammatory diseases, consistent changes were observed for a signature associated with neutrophil activation/inflammation. This transcriptional signature most resembled that of subjects with Kawasaki disease.ConclusionsThe similarities observed between psoriasis and Kawasaki disease blood transcriptome signatures suggest that immune mechanisms driving the pathogenesis of these diseases may be at least partially shared. This notion is reinforced by case reports describing the development of psoriasis disease in patients with Kawasaki disease. Potential implications for novel therapeutic approaches, including the repurposing of biologic drugs targeting IL17 or its receptor for the treatment of Kawasaki disease are discussed.


2020 ◽  
Author(s):  
Darawan Rinchai ◽  
Basirudeen Kabeer ◽  
Mohammed Toufiq ◽  
Zohreh Calderone ◽  
Sara Deola ◽  
...  

SUMMARYCovid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: therapeutic development relevance, SARS biology relevance and immunological relevance. Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients.


2020 ◽  
Author(s):  
Anbarasu Karthikaichamy ◽  
John Beardall ◽  
Ross Coppel ◽  
Santosh Noronha ◽  
Sanjeeva Srivastava ◽  
...  

ABSTRACTMicroalgae can tolerate a wide range of environmental conditions and have been exploited for their lipid and carbohydrate accumulating properties. The utility of this process could be further enhanced through understanding the critical gene regulatory networks that govern the acclimatization process. Advancements in systems biology and sequencing tools now enable us to obtain a genome-wide overview of gene expression under particular conditions of interest. Under salinity stress, Microchloropsis gaditana CCMP526, a commercially important alga has been previously reported to accumulate carbohydrate and lipid. To understand the mechanism of acclimatization, here we report a temporal transcriptomic analysis of M. gaditana under two different salinity levels (55 and 100 PSU). The short term (0, 1 and 6 h) and long term (24 and 72 h) responses of the salt-induced transcript pool were used to identify salinity-inducible genes using correspondence analysis. The transcript abundance of genes involved in triacylglycerol biosynthesis, membrane lipid modification, carbon assimilation and shunting, and osmolyte biosynthesis indicated that M. gaditana employs a two-stage acclimatization strategy during hypersaline conditions.


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