Monthly Archives: October 2020

Genetics

Writing Assignment 3

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Write a Summary of a Primary Article

Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the members of the Coronaviridae family, along with its predecessor SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV). SARS and MERS have high case fatality rates (CFR) at 9% and 36% respectively. CoV-2, (COVID-19) is more infectious tha the previously mentioned viruses, but has a much lower CFR. Th closest genetic relative to CoV-2 is to bat coronavirus. These three strains are dependent on zoonotic transmission from animals, such as camels and bats, to humans.

            It was hypothesized that high-CRF strains were more pathogenetic due to similar genomic determinants. Human coronaviruses span two genera, Alphacoronavirus and Betacoronavirus. Reduction analysis showed a clustering of SARS separately from the other coronaviruses. MERS was spread between the two clusters as an intermediate between the high-CFR and low-CFR strains. This implied that the CFR trait impacts the clustering by deletions and insertions. The high-CFR strains share a common ancestor and may have emerged from the high CFR or evolved independently in different strains.  

            Machine learning was used to detect regions that show clean separation between high- and low-CFR genomes. The results were evaluated by cross-validation and filtered to find genomic regions that distinguish high- and low-CFR. This allows automatic detection of regions that are not easily distinguished. From this method, 11 regions of nucleotide alignments that are predictive of high-CFR to be identified. These regions occurred in pp 1 ab, spike glycoprotein, membrane glycoprotein, and nucleocapsid.

            The identified regions revealed that deletions and insertions result in substantial enhancement of motifs that determine nuclear localization in high-CFR. During evolution, coronavirus had stronger nuclear localization and export signals from clades that included high-CFR viruses and strains from animals, mainly bats, shown by increased positive charge of the amino acids making up the nuclear localization signals. The increasing charge could affect the functions of genomic RNA and the M protein. Localization of the nucleocapsid protein to the nucleoli has been reported and associated with pathogenicity.

            In the study of genomic features that associate with the transmission of coronaviruses from animal to human, they identified independent insertion from the three viruses in the spike glycoprotein, mainly the receptor-binding domain. However, no sequence similarity was found between SARS, MERS, and CoV-2 strains which may indicate independent evolution. Despite this, the inserted segments in the strains contained a proline-cystine (PC) doublet. In both SARS and MERS, the insert acts directly with the respective receptors but the interactions differ. MERS has a salt bridge and hydrophobic interaction while SARS and CoV-2 have a hydrophobic interaction. The flexibility gained by the receptor-binding domain could allow the spike glycoprotein to be more malleable to bind to a receptor and allowing zoonotic transmission. MERS inserts are more rigid and may explain the virus to not fully adapt to human-to-human transmission. These features conclude that the ongoing evolution of SARS-CoV-2 can allow for more highly pathogenic strains to be transmitted to humans.

Gussow AB, Auslander N, Faure G, Wolf YI, Zhang F, Koonin EV. Genomic determinants of pathogenicity in SARS-CoV-2 and other human coronaviruses. Proc Natl Acad Sci U S A. 2020;117(26):15193-15199. doi:10.1073/pnas.2008176117

Genetics

Writing Assignment 1

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Primary vs Review Articles: Which is Which?

Kira Amidon

CRN: 21701

Dr. Janet Rinehart-Kim

            A primary article is a scientific paper written by the authors of the experiment. It usually includes an introduction, purpose of the experiment, the methods used in the experiment, the results from the trials, a discussion about what the data proves or disproves, and references for any outside information used. A primary article usually has been submitted for peer review before final publication. The only summarization in a primary article is typically in the abstract of the paper before the introduction.

            A review article is a scientific paper that summarizes the data from the primary articles. Review articles are written by authors who have read the data and summarize the findings into a digestible article that mainly consists of the conclusions and theories of the possible connections of the research to a problem. Review articles will include a link to the original article and are considered secondary articles. These are best used for finding information relevant to your topic quickly.

            The peer review process is a quality control process used to verify legitimacy of scientific papers. The document is sent to a team of scientists in the same field to be examined for errors and incontinuities. It also checks for originality in the field and determines significance of the findings. The peer review process can involve a single-blind review, where reviewers know the authors’ identity or a double-blind review where both the identity of the reviewers and the authors are unknown to eliminate bias. Then there is open peer review where critiques do not have anonymity on their review of the article.

            The primary article is “Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus.” The article lists only empirical data from the research of the authors. The “Bat Coronaviruses in China” article is heavily summarized and does not use first person language. It also states that it is a review and brings together data used in other studies and gives theories of how to use this data in further research.