Highlights from Genomic Research Live

Advances in next-generation sequencing technology have promoted the development of genetics studies, resulting in major scientific discoveries in the field of life science. To make it easier for researchers worldwide to keep up with the latest research achievements, Novogene has been offering “Genomic Research Live,” a professional and dedicated online sharing and exchange platform for life scientists throughout the world since the beginning of 2022.

We’ve had a blast and showcased cutting-edge results from our partners’ collaborative efforts in the last two months. In these four excellent sharing sessions, we probed cytidine deaminase’s function and characteristic role through in-depth transcriptomic analysis, understood lychee flowering regularity and history through genome sequencing decoding, traced the history of the endangered Chinese crocodile lizard through population genomics, and elaborated the association between fine particulate matter and asthma through RNA sequencing. Now, let us beam back to those highlights!

Addressing the new role of Cytidine Deaminase in pancreatic cancer using transcriptomics

We invited Dr. Pierre Cordelier, a Ph.D. in Human Physiopathology, as our first speaker; In this webinar he shared his research into the role of cytidine deaminase in Pancreatic Cancer, explored the potential therapeutic interventions to defeat tumor resistance to treatment with us. The hallmarks of cancer that not only fuel oncogenesis but also play a significant role in tumor diversity are DNA replication stress and genome instability. Pancreatic cancer is highly lethal and asymptomatic. It is usually diagnosed at the advanced stages. Pancreatic tumors are very complex at the cellular levels, and distant metastasis occurs in almost 90% of patients. Therefore they are hard to treat. Microscopic non-invasive epithelial proliferation in the pancreatic ducts, known as pancreatic intraepithelial neoplasias, constitutes a significant cause of pancreatic cancer. Gemcitabine has been used as first-line chemotherapy for pancreatic cancer since 1997. From the experimental knowledge, it is proven that the CDA is overexpressed explicitly in PDAC tumors. It determines the cellular toxicity of gemcitabine. In pancreatic cancers, CDA expression is linked to a poor prognosis. Gemcitabine is protected from tumor cells by CDA. Inhibiting CDA instead of treating the tumor cells with gemcitabine is more effective in reducing tumor growth. CDA’s deaminase activity is responsible for its ability to reduce replication stress in pancreatic cancer. Pancreatic tumors with high CDA levels support more genetic instability than tumors with low CDA. Tumor needs genomic instability for their growth. The drugs targeting DNA synthesis aim to produce high levels of genetic instability in cancer that even the cell itself can’t bear the damage it causes and eventually dies. Tumor cells with high CDA expression might better resist treatment with the drugs targeting DNA synthesis. The experimental data shows that the findings provide us with in-depth knowledge of mechanisms by which pancreatic cells control replication stress—targeting CDA as a potential therapeutic intervention to defeat tumor resistance in pancreatic tumors.

The domestication history of lychee and its flowering regulation decoded by full genome sequencing

One of the unique tropical fruits is the Lychee. It has a distinct appearance and a delectable flavor and belongs to the Sapindaceae family. In order to get novel insights into the domestic history of Lychee, decoding of the haplotypic genome is required. This time, Dr. Xia Rui, a professor at South China Agricultural University, shared his research about the domestication history of Lychee and its flowering regulation as decoded by full genome sequencing. The decoding of the haplotypic genome also helps develop an in-depth understanding of the genetics of flowering regulation. In this research, researchers created 15 pseudo-chromosome assemblies of the genome—the genome of the cultivar of a total of 470 Mb. Two haplotypic assemblies of high heterozygosity with 13,517 allelic genes were expressed in different tissues. Two independent domestic events were confirmed by analyzing 72 re-sequenced Lychee accession. The haplotype domesticated from the wild population in Yunnan was aligned to extremely early maturing cultivars (EEMC). At the same time, the other haplotype domesticated from the wild population in Hainan were aligned with late-maturing cultivars (LMC). The early maturing cultivars were developed from hybridization between EEMC and LMC individuals in Guangdong. The CONSTANT-like genes in the genome controlled the fruit maturation differences among lychee cultivars. So from this analysis, one can get an in-depth understanding of the natural history of crop domestication. And this data is just the hit the nail on the head for improving crops, especially Lychee. Hence, by re-sequencing the genome, one can restore the original domestication and cultivation of Lychee and develop an understanding of uncovered critical genes involved in lychee fruit maturation.

Population genomics of the endangered Chinese crocodile lizard

Shinisaurus crocodilurus is a semi-aquatic, viviparous, and relict species of its family. In order to resolve the population history of the endangered Chinese crocodile lizard, genomic studies were conducted. In the third webinar, Hongxin Xie, a Ph.D. candidate in Prof.Weiguo Du’s lab, explained how genetic purging works in small wild populations with Chinese crocodile lizards as a case and shares the importance of genetic diversity in conservation biology.

Genomic studies help track back the history of the specie but also explain clearly how genetic purging work even in small populations. It is commonly hypothesized that deleterious gene purging mitigates the inbreeding depression, but there is no valid hypothesis on its effectiveness in the case of endangered species. By analyzing the genome of endangered Chinese lizards, we get deep insights into how the purging of deleterious genes in a contracted population occurs. In Conservation biology, the small population paradigm is the most important one that provides information about the fragmented population. In a fragmented population, the loss of genetic diversity and increased inbreeding will reduce the whole population’s fitness. Hence the reduction in population size eventually leads to an extinction vortex. Four genetically conserved units with a sharp decrease in their population size and genetic diversity were revealed after the population genomic studies. By conducting a genomic simulation, it was confirmed that the effective purging of deleterious alleles occurs in the contracting population. Comparing the relative genetic loads also support the statement further. The genomic simulation predicted that the prolonged bottlenecking resulted in the gradual accumulation of deleterious alleles. Hence the genomic studies depict the significance of functional genetic diversity in fragmented populations.

Fine particulate matter and childhood asthma

One of the common chronic respiratory disorders is asthma. It is characterized by respiratory tract hyperresponsiveness. It is a global health problem affecting 385 million individuals. The crucial type of allergen known as s fine particulate matter is the main risk factor for acute asthma attacks in children. These fine particulate are less than 2.5 μm in diameter (PM2.5). The mechanism explaining the association between the fine particulate and asthma is still unclear. Dr. Rui Zheng, a lecturer at Nanjing Medical University, explored this biological process with us in this webinar. This study is focused on PM2.5-treated HBE cells-secreted extra-cellular vesicles (PM2.5-EVs). This fine particulate increases longitudinal sensitive human bronchial smooth muscle cells (HBSMCs). These also cause cytotoxicity in horizontal HBE cells. The let-7i-5p was significantly overexpressed in PM2.5-EVs and asthmatic plasma. RNA-seq results showed that the EV-packaged let-7i-5p and the biomarker IgE depicted the best diagnostic activity. The let-7i-5p was packaged into PM2.5-EVs by interacting with ELAVL1a to activate the MAPK signaling pathway by suppressing target DUSP. The asthma symptoms were aggravated by injection of EV-packaged let-7i-5p. Hence, plasma-packaged let-7i-5p is the unique predictor of childhood asthma.

The above is a synopsis of our previous four sharing sessions. Novogene will strive to bring you more cutting-edge sharing of exciting gene sequencing technologies to stimulate the scientific research potential of our global research colleagues and promote the sustainable development of life sciences. We hope that by using this online sharing form, more researchers will be able to comprehend the use of NGS in genomics research. Let’s venture together into the world of genomics! Feel free to visit Novogene Online Events for more information.