Baez, E. | bioRxiv Science

bioRxiv2020

Complex networks of miRNA-transcription factors mediate gene dosage compensation in aneuploid cancer

Cancer complexity is consequence of enormous genomic instability leading to aneuploidy, a hallmark of most cancers. We hypothesize that dosage compensation of critical genes could arise from systems-level properties of complex networks of microRNAs (miRNA) and transcription factors (TF) as a way for cancer cells to withstand the negative effects of aneuploidy. We studied gene dosage compensation at the transcriptional level on data of the NCI-60 cancer cell line panel with the aid of computational models to identify candidate genes with low tolerance to variation in gene expression despite high variation in copy numbers. We identified a network of TF and miRNAs validated interactions with those genes to construct a mathematical model where the property of dosage compensation emerged for MYC and STAT3. Compensation was mediated by feedback and feed-forward motifs with 4 miRNAs and was dependent on the kinetic parameters of these TF-miRNA interactions, indicating that network analysis was not enough to identify this emergent property. The inhibition of miRNAs compensating MYC suggest a therapeutic potential of targeting gene dosage compensation against aneuploid cancer.

systems biology↗

bioRxiv2019

{-}{-}Genome wide association study reveals novel candidate genes associated with productivity and disease resistance to Moniliophthora spp. in cacao (Theobroma cacao L.)

Cacao (Theobroma cacao L.), the source of chocolate, is one the most important commodity products for farmers to improve their economic benefits. However, diseases such as frosty pod rot (FPRD) caused by Moniliophthora roreri and witches broom (WBD) caused by Moniliophthora perniciosa, limits the increase in yields. Molecular tools can help to develop more rapidly cacao varieties with disease resistance. In the present study, we sequenced by genotyping-by-sequencing (GBS), 229 cacao accessions to examine their genetic diversity and population structure. From those accessions, 102 have been evaluated for disease resistance and productivity to conduct a genome-wide association study (GWAS) based on 9,003 and 8,131 SNPs recovered by mapping against to the annotated cacao genomes (Criollo and Matina). Three promissory accessions for productivity and 10 accessions showing good tolerance to the evaluated diseases were found in the phenotypic evaluation. The work presented herein provides the first association mapping study in cacao using SNP markers based on GBS data. The GWAS identified two genes associated to productivity and seven to disease resistance. The results enriched the knowledge of the genetic regions associated to important traits in cacao that can have significant implications for conservation and breeding strategies such as marker-assisted selection (MAS).

genetics↗