Progress 01/01/16 to 12/31/18
Outputs Target Audience:Genome research, education and service community; Animal breeding and genetics companies; Livestock producers, processors and retailers; Biomedical and model organism community; Veterinarians; Livestock judges and fair management. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Three undergraduate students, two graduate students and two visiting scholars received mentored training opportunities in both dry and wet lab settings. How have the results been disseminated to communities of interest?Some of the results from this funded project have been disseminated through the classroom in undergraduate and/or graduate courses at Washington State University. Our results have been shared with the scientific communities and livestock industries through international, national and local conferences/workshops/seminars, as well as through peer-reviewed publications. In particular, we have published our outreach article in the leading science communication publication, Scientia. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts What was accomplished under these goals?
Impacts Changes in Knowledge: Alternative transcripts, rather than genes are minimal functional units in genomes. Changes in Technology: WTTS-seq (whole transcriptome termini site sequencing) and WTSS-seq (whole transcriptome start site sequencing) are sensitiveand powerfulto reveal transcriptome networks specific to phenotypic changes. Changes in Condition: Mapping of alternative promoter, splicing and polyadenylation plus RNA editing (epitranscriptome)is essential to understand animal genome functions in health and diseases. For Objective #1, we were able to collect 203,503 alternative polyadenylation (APA) sites in cattle. The collection was based on ten types of bovine cells/tissues/organs using our whole transcriptome termini site sequencing method. Among them, 137,359 sites were assigned to 20,801 currently annotated bovine genes. We observed that APA use frequencies, site-types and genomic neighborhoods were significantly different (p < 2.2e-16) among gene biotypes. There were 1.06, 1.35, 1.59, 2.82 and 7.62 APA sites per gene in average for tRNAs (transfer RNAs), miRNAs (microRNAs), pseudogenes, lncRNAs (long non-coding RNAs) and protein coding genes, respectively. Distal sites were used 50 - 70% of the time by tRNAs and miRNAs, while lncRNAs and protein coding genes used intronic APA sites 60% of the time. In comparison, pseudogenes used exonic APA sites most frequently. APA sites were located in A-rich stretch neighborhoods in 15%, 17%, 28%, 36% and 40% of tRNAs, miRNAs, lncRNAs, protein coding genes and pseudogenes, respectively. For Objective #2, we observed that pathways were enriched for cell cycle and division when satellite cells were cultured in growth medium for 48 h, but were enriched for muscle development and adaption pathways when cells were cultured in differentiation medium. Pathways with upregulated APAs in tissues collected from Angus cattle were related to muscle growth, development and function, but were associated with negative regulation of cell differentiation and xenobiotic metabolic process in Wagyu tissues. Endometrial epithelial cells from healthy Holstein cows had upregulated APAs enriched in pathways linked to cilium function, compared to cows with endometritis that had enriched pathways involved in immune and inflammation. Overall, profiling APA events reveals molecular mechanisms involved in growth, development and health/disease status.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Brutman JN, Zhou X, Zhang Y, Michal J, Stark B, Jiang Z, Davis JF. 2018. Mapping diet- induced alternative polyadenylation of hypothalamic transcripts in the obese rat. Physiol Behav. 188:173-180.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Zhang SW, Zhang YZ, Zhou X, Fu X, Michal JJ, Ji GL, Du M, Davis JF, Jiang Z. 2018. Alternative polyadenylation drives genome-to-phenome information detours in the AMPKA1 and AMPKA2 knockout mice. Sci Rep. 8:6462.
- Type:
Journal Articles
Status:
Published
Year Published:
2018
Citation:
Zhang YQ, Carrion SA, Zhang YZ, Zhang XH, Zinski AL, Michal JJ, Jiang Z. 2018. Alternative polyadenylation analysis in animals and plants: newly developed strategies for profiling, processing and validation. Int J Biol Sci. 14(12):1709-1714.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Jiang Z. 2019. RNA and the key to the diversity of life. Scientia (https://doi.org/10.26320/SCIENTIA312).
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Zhou X, Zhang YZ, Michal JJ, Qu LJ, Zhang SW, Wildung MR, Du W, Pouchnik DJ, Zhao H, Xia Y, Shi HH, Ji GL, Davis JF, Smith GD, Griswold MD, Harland RM, Jiang Z. 2019. Alternative polyadenylation coordinates embryonic development, sexual dimorphisms and longitudinal growth in Xenopus Tropicalis. Cell Mol Life Sci. 2019 Feb 7. doi: 10.1007/s00018-019-03036-1. [Epub ahead of print].
- Type:
Journal Articles
Status:
Submitted
Year Published:
2019
Citation:
Stotts MJ, Zhang YZ, Zhang SW, Michal JJ, Velez JS, Hans B, Maquivar M, Jiang Z. Alternative polyadenylation events in epithelial cells sense endometritis progression in dairy cows.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Stotts MJ, Zhang YZ, Zhang SW, Michal JJ, Velez J, Hans B, Maquivar M, Jiang Z. 2018. Alternative polyadenylation events in epithelial cells serve as decisive sensors for endometritis progression in dairy cows. ASAS-CSAS Joint Meeting 2018, Vancouver, Canada.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Jiang Z, Zhou X, Zhang YZ, Michal JJ, Qu LJ, SW, Wildung MR, Du WW, Pouchnik DJ, Zhao H, Xia Y, Shi HH, Ji GL, Davis JF, Harland RM. 2018. Profiling of alternative polyadenylation: the newest genomic resource for functional annotation of the Xenopus tropicalis genome. 17th International Xenopus Conference, Seattle, USA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Jiang Z. The central role of RNA in understanding of the central dogma. FAANG Workshop (01/12/2018). Plant and Animal Genome Conference XXVI. 01/13 01/17, 2018. San Diego, USA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Jiang Z. The rules of life via alternative polyadenylation. School of Molecular Biosciences Fall Seminar Series, 10/11/2018, WSU.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Jiang Z. Will alternative polyadenylation profiling revolutionize the clinical diagnosis field? 4th Annual Next Generation Sequencing and Clinical Diagnostics & Single Cell Analysis USA Congress, 10/23 10/24/2018, Boston.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Jiang Z. Genome to phenome: amplification of DNA function via alternative transcriptome. BITs World DNA and Genome Day 2019, 25 27 April 2019, Nanjing, PR China.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2019
Citation:
Jiang Z, Michal JJ, Zhou X, He SG, Stotts MJ, Zhang YQ, Zhang XH, Leng XY, Zhang YZ, Wang HY, Jiang HL, Du M, Maquivar M, Fox LK. 2019. Genome wide mapping of over 200,000 alternative polyadenylation sites in cattle. 37th International Society for Animal Genetics Conference, July 7 12, Lleida, Spain.
- Type:
Conference Papers and Presentations
Status:
Submitted
Year Published:
2019
Citation:
Zhou X, Fu X, Zhang YZ, Zhang SW, Michal JJ, Wang HY, Du M, Jiang Z. 2019. Up-regulation of wound healing pathway may trigger adipogenic potentials of intramuscular progenitor cells in Wagyu as compared to Angus cattle. 2019 ASAS-CSAS Annual Meeting and Trade Show, July 8 11, Austin, TX, USA.
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Progress 01/01/17 to 12/31/17
Outputs Target Audience:Genome research, education and service community; Animal breeding and genetics companies; Livestock producers, processors and retailers; Veterinarians; Livestock judges and fair management. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?The funded project has provided opportunities to train one postdoctoral fellow, one Ph.D. student, two M.Sc. students, two undergraduate students and two visiting scholars. How have the results been disseminated to communities of interest?In addition to three talks presented at the Non-coding RNA workshop, Swine Workshop and FAANG workshop in early January 2017 at the Plant and Animal Genome Conference, we have spoken about our work on alternative polyadenylation with colleagues, graduate students and undergraduate students in animal, veterinary, food and plant science areas. In particular, a plenary talk was given to approximately 2,000 participants at the 19th Chinese National Conference on Animal Breeding and Genetics, October 2017 in Nanjing, China. What do you plan to do during the next reporting period to accomplish the goals?We will 1) construct a large number of WTTS-seq libraries to collect, characterize and complete our first APS resources in cattle; 2) collaborate with the FAANG community to further broaden the application of WTTS-seq and WTSS-seq methods; 3) try to publish our results in peer reviewed journals with high impact factors; 4) present our work at different workshops and conferences and plan our first Pacific Spring Symposium in 2018 and 5) submit our data to various public databases.
Impacts What was accomplished under these goals?
We have continued our efforts to generate alternative polyadenylation site (APS) resources for cattle. After sequencing new WTTS-seq libraries, we have evidence to show that there are at least 118,788 APSs with 25 reads per site harbored in the bovine genome. We have upgraded our bioinformatics pipelines for data analysis, including read quality control using the FASTX Toolkit (http://hannonlab.cshl.edu/fastx_toolkit/), trimming with in-house Perl scripts, mapping using TMAP (version 3.4.1, https://github.com/iontorrent/TMAP) and characterization using the Cuffcompare program. A total of 241 samples were collected from pure Angus, full Wagyu and their crossbreds. Tissues/organs included liver, muscle, heart, lung, kidney, spleen, tongue, rumen, visceral fat, subcutaneous fat, endometrium, ovary, testes parenchyma, and epididymis. Endometrial cells from 33 cows with different health status (healthy and sub-clinical endometritis) before and after treatment with dextrose were also collected. In order to broaden the impact of our work, we have collaborated with various groups or expanded the application of our WTTS-seq method to different species, such as mouse (knockout models), rat (nutrigenomics), chicken (gender difference) and X. tropicalis (embryo development).
Publications
- Type:
Journal Articles
Status:
Under Review
Year Published:
2017
Citation:
Brutman JN, Zhou X, Zhang YZ, Michal JJ, Stark B, Jiang Z, Davis JF. 2017. Mapping diet-induced alternative polyadenylation in the hypothalamus of male rats.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Jiang Z. Invited Seminar. Coding and non-coding genes: striking differences in use of alternative polyadenylation sites. College of Animal Sciences and Technology, Nanjing Agricultural University. 03/05/2017. Nanjing, China.
- Type:
Journal Articles
Status:
Published
Year Published:
2017
Citation:
Zhou X, Michal JJ, Jiang Z, Liu B. 2017. MicroRNA expression profiling in alveolar macrophages of indigenous Chinese Tongcheng pigs infected with PRRSV in vivo. J Appl Genet. 58(4):539-544.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Jiang Z. Invited Seminar. Transcriptome Complexity and Complex Environment-Host-Pathogen Relationships. College of Veterinary Medicine, Nanjing Agricultural University. 03/13/2017. Nanjing, China.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Jiang Z. Invited Seminar. Alternative Polyadenylation: A Conserved Phenomenon from Animals to Plants. Heilongjiang Academy of Agricultural Sciences. 07/18/2017. Harbin, China.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Jiang Z. Invited Seminar. Foodomics, Biomedicine and Human Health. College of Food Sciences, Nanjing Agricultural University. 10/10/2017. Nanjing, China.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Jiang Z. Invited plenary speaker. Antagonistic genomics, epigenome editing and animal improvement. 19th Chinese National Conference on Animal Breeding and Genetics. 10/13 10/16, 2017. Nanjing, China.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Jiang Z. Invited Seminar. Transcriptome diversity and complex phenotypes. College of Animal Sciences and Veterinary Medicine, Huazhong Agricultural University. 10/18/2017. Wuhan, China.
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Progress 01/01/16 to 12/31/16
Outputs Target Audience:Genome research community, cattle industry Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?The funded project has provided opportunities to train one postdoctoral fellow (Dr. Xiang Zhou), three Ph.D. students (Mr. Rui Li, Ms. Shuwen Zhang and Mr. Hussain Alabdullah) and two M.Sc. students (Ms. Yangzi Zhang and Ms. Megan Stotts). In addition, two professors from China are currently at Washington State University for 6 months of training. We anticipate that another research scientist will be coming soon from China. How have the results been disseminated to communities of interest?First, we have made it possible for the public to freely access our WTTS-seq method from the Genetics Journal website or NCBI PubMed search. Second, we spoke at the Swine Genome Workshop, Plant and Animal Genome Conference and shared our experience in library preparation and troubleshooting. Third, we presented a poster at the 35th International Animal Genetics conference and illustrated our WTTS-seq in detail. What do you plan to do during the next reporting period to accomplish the goals?We will 1) finalize our pipelines for mapping, clustering and analyzing APSs in cattle; 2) continue to collect samples for library preparation and sequencing, 3) initiate broader collaborative networks for use of our techniques in functional analysis of animal genomes; 4) present our work at various conferences and 5) submit our sequencing data to the NCBI Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo/) databases.
Impacts What was accomplished under these goals?
Our initial collection shows that there are at least 75,438 alternative polyadenylation sites (APSs) or alternative transcripts harbored in the bovine genome. Among them, 66,702 APSs are assigned to 14,442 currently annotated genes in the species. First, APS usage differs by gene biotype. There were only 1.07 and 1.31 APSs per gene in tRNA and miRNAs, respectively. Moderate APS usage was observed in pseudogenes and lncRNAs, being 1.63 and 2.28 APSs per gene, respectively. In contrast, protein coding genes contained an average of 4.99 APSs per gene. Second, genomic regions downstream of APSs have distinct nucleotide composition patterns. Based on adenosine (A) contents, APSs can be classified into two major categories: A-rich stretches with 37,122 APSs and non-A-rich stretches with 38,316 APSs. Third, APS usage in introns is common. Among 63,092 APSs assigned to protein coding genes, 29,592 (46.90%) were intronic APSs. We believe that the unique APS resources produced in the funded project will aid in annotation of the bovine genome and transcriptome for understanding multi-functions of genes in the species.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2016
Citation:
Zhou X, Li R, Michal JJ, Wu XL, Liu Z, Zhao H, Xia Y, Du W, Wildung MR, Pouchnik DJ, Harland RM, Jiang Z. 2016. Accurate profiling of gene expression and alternative polyadenylation with whole transcriptome termini site sequencing (WTTS-Seq). Genetics. 203(2): 683-697.
- Type:
Journal Articles
Status:
Under Review
Year Published:
2017
Citation:
Zhou X, Michal JJ, Zhang Y, Harland RM, Jiang Z. 2017. Gender differences in transcriptome-wide usage of alternative polyadenylation sites. Scientific Reports
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Zhou X, Li R, Michal JJ, Wu X-L, Liu ZZ, Zhao H, Xia Y, Harland RM, Jiang Z. 2016. Whole transcriptome termini site sequencing (WTTS-seq): a next generation sequencing method to accurately profile gene expression and alternative polyadenylation with one pipeline. 35th International Society for Animal Genetics Conference, July 23-27, 2016, Salt Lake City, Utah, USA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Jiang Z, Zhou X, Michal JJ, Li R, Harland RM. What factors jeopardize whole transcriptome analysis using next generation sequencing approaches? Swine Workshop Presentation. Plant and Animal Genome Conference XXIV. 01/09 01/13, 2016. San Diego, USA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2016
Citation:
Jiang Z. Whole transcriptome termini site sequencing: advantages over RNA sequencing. Invited Seminar. College of Veterinary Sciences, Nanjing Agricultural University. 05/18/2016. Nanjing, China.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2017
Citation:
Zhou X, Michal JJ, Zhang Y, Harland RM, Jiang Z. Whole transcriptome termini site sequencing reveals gender differences in genome-wide usage of alternative polyadenylation sites. Swine Workshop Presentation. Plant and Animal Genome Conference XXV. 01/14 01/18, 2017. San Diego, USA.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2017
Citation:
Zhou X, Zhang Y, Brutman JN, Michal JJ, Jiang HL, Wang Y, Ross PJ, Delany ME, Zhou HJ, Cheng HH, Davis JF, Jiang Z. Non-coding RNAs: striking features in use of alternative polyadenylation sites. No-coding RNA Workshop Presentation. Plant and Animal Genome Conference XXV. 01/14 01/18, 2017. San Diego, USA.
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2017
Citation:
Jiang Z. Alternative polyadenylation and multi-functions of genes. FAANG Workshop Presentation. Plant and Animal Genome Conference XXV. 01/14 01/18, 2017. San Diego, USA.
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