Banca de QUALIFICAÇÃO: THAÍS DE ALMEIDA RATIS RAMOS

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : THAÍS DE ALMEIDA RATIS RAMOS
DATE: 21/02/2020
TIME: 10:00
LOCAL: BioME
TITLE:

Biologia de sistemas de células individuais de RNAs não codificantes longos associados com o desenvolvimento do tecido cardíaco e com doenças cardiovasculares

KEY WORDS:

heart development, lncRNAs, single-cell, systems biology, co-expression

PAGES: 70
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Long non-coding RNAs (lncRNAs) comprise the most representative transcriptional units of the mammalian genome and are known to be associated with organ development. Thus, we decided to study heart development since cardiovascular diseases are responsible for the death of 17.9 million people each year, an estimated 31% of all deaths worldwide, according to World Health Organization (WHO). Here, we used a combination of Gencode (M20), Ensembl (GRCm38.95) and Amaral et al (2018) transcripts to define the set of non-redundant reference lncRNAs; and Gencode (M20) as reference coding transcripts. Furthermore, we used the public single-cell transcriptome dataset from DeLaughter et al (2016), which generated data for 4 embryonic (E9.5, E11.5, E14.5, E18.5) and 4 postnatal (P0, P3, P7, P21) stages from mus musculus model organism. We mapped the transcripts and used an expression filter (FPKM > 0.001) and a percentage of expressed cells considering the expression of transcripts in at least 5% of the cells. After this, we performed a feature selection and we found the differential expressed transcripts. Then, we used the silhouette method to estimate the best number of clusters, hierarchical clustering to group the cells, PCA to reduce the dimensionality and t-SNE for clusters visualization. Furthermore, we used cell types markers genes to assign the clusters cell types, chi-squared and adherence tests to observe the cluster's significations (p-value < 0.05) and then we observed the co-expression. We used 5 different areas of the heart during development: ventricle, atrium, left ventricle, right ventricle and left atrium. About cell clusters, we were able to identify 8 distinct cells types: cardiomyocytes; myoblasts; endothelial; mural, vascular smooth muscle and pericytes cells; fibroblasts and myofibroblasts; t-cells; macrophages and monocytes; and dendritic. Moreover, we identified novel markers transcripts divided into coding genes and different types of lncRNAs. The systems biology analyses identified co-expression modules linked to heart development. As future work, we intend to acquire functional roles of these RNAs in cardiac tissue development using experimental validation approaches.

BANKING MEMBERS:
Interno - 1513597 - JOAO PAULO MATOS SANTOS LIMA
Interno - 1507794 - RODRIGO JULIANI SIQUEIRA DALMOLIN
Presidente - 012.117.554-52 - THAIS GAUDENCIO DO REGO - UFPB
Interno - 052.739.204-93 - VINICIUS RAMOS HENRIQUES MARACAJA COUTINHO - USP