Posts Tagged ‘phylogenetic trees’

Emergence of a new SARS-CoV-2 variant from GR clade with a novel S glycoprotein mutation V1230L in West Bengal, India

Authors: Rakesh Sarkar, Ritubrita Saha, Pratik Mallick, Ranjana Sharma, Amandeep Kaur, Shanta Dutta, Mamta Chawla-Sarkar

Reporter and Original Article Co-Author: Amandeep Kaur, B.Sc. , M.Sc.

Since its inception in late 2019, SARS-CoV-2 has evolved resulting in emergence of various variants in different countries. These variants have spread worldwide resulting in devastating second wave of COVID-19 pandemic in many countries including India since the beginning of 2021. To control this pandemic continuous mutational surveillance and genomic epidemiology of circulating strains is very important. In this study, we performed mutational analysis of the protein coding genes of SARS-CoV-2 strains (n=2000) collected during January 2021 to March 2021. Our data revealed the emergence of a new variant in West Bengal, India, which is characterized by the presence of 11 co-existing mutations including D614G, P681H and V1230L in S-glycoprotein. This new variant was identified in 70 out of 412 sequences submitted from West Bengal. Interestingly, among these 70 sequences, 16 sequences also harbored E484K in the S glycoprotein. Phylogenetic analysis revealed strains of this new variant emerged from GR clade (B.1.1) and formed a new cluster. We propose to name this variant as GRL or lineage B.1.1/S:V1230L due to the presence of V1230L in S glycoprotein along with GR clade specific mutations. Co-occurrence of P681H, previously observed in UK variant, and E484K, previously observed in South African variant and California variant, demonstrates the convergent evolution of SARS-CoV-2 mutation. V1230L, present within the transmembrane domain of S2 subunit of S glycoprotein, has not yet been reported from any country. Substitution of valine with more hydrophobic amino acid leucine at position 1230 of the transmembrane domain, having role in S protein binding to the viral envelope, could strengthen the interaction of S protein with the viral envelope and also increase the deposition of S protein to the viral envelope, and thus positively regulate virus infection. P618H and E484K mutation have already been demonstrated in favor of increased infectivity and immune invasion respectively. Therefore, the new variant having G614G, P618H, P1230L and E484K is expected to have better infectivity, transmissibility and immune invasion characteristics, which may pose additional threat along with B.1.617 in the ongoing COVID-19 pandemic in India.

Reference: Sarkar, R. et al. (2021) Emergence of a new SARS-CoV-2 variant from GR clade with a novel S glycoprotein mutation V1230L in West Bengal, India. medRxiv. https://doi.org/10.1101/2021.05.24.21257705https://www.medrxiv.org/content/10.1101/2021.05.24.21257705v1

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A New Computational Method illuminates the Heterogeneity and Evolutionary Histories of cells within a Tumor, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 1: Next Generation Sequencing (NGS)

A New Computational Method illuminates the Heterogeneity and Evolutionary Histories of cells within a Tumor

Reporter: Aviva Lev-Ari, PhD, RN


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Numerous computational approaches aimed at inferring tumor phylogenies from single or multi-region bulk sequencing data have recently been proposed. Most of these methods utilize the variant allele fraction or cancer cell fraction for somatic single-nucleotide variants restricted to diploid regions to infer a two-state perfect phylogeny, assuming an infinite-site model such that each site can mutate only once and persists. In practice, convergent evolution could result in the acquisition of the same mutation more than once, thereby violating this assumption. Similarly, mutations could be lost due to loss of heterozygosity. Indeed, both single-nucleotide variants and copy number alterations arise during tumor evolution, and both the variant allele fraction and cancer cell fraction depend on the copy number state whose inference reciprocally relies on the relative ordering of these alterations such that joint analysis can help resolve their ancestral relationship (Figure 1). To tackle this outstanding problem, El-Kebir et al. (2016) formulated the multi-state perfect phylogeny mixture deconvolution problem to infer clonal genotypes, clonal fractions, and phylogenies by simultaneously modeling single-nucleotide variants and copy number alterations from multi-region sequencing of individual tumors. Based on this framework, they present SPRUCE (Somatic Phylogeny Reconstruction Using Combinatorial Enumeration), an algorithm designed for this task. This new approach uses the concept of a ‘‘character’’ to represent the status of a variant in the genome.

Commonly, binary characters have been used to represent single-nucleotide variants— that is, the variant is present or absent. In contrast, El-Kebir et al. use multi-state characters to represent copy number alterations, which may be present in zero, one, two, or more copies in the genome.

SPRUCE outperforms existing methods on simulated data, yielding higher recall rates under a variety of scenarios. Moreover, it is more robust to noise in variant allele frequency estimates, which is a significant feature of tumor genome sequencing data. Importantly, El-Kebir and colleagues demonstrate that there is often an ensemble of phylogenetic trees consistent with the underlying data. This uncertainty calls for caution in deriving definitive conclusions about the evolutionary process from a single solution.”

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From Original Paper

Inferring Tumor Phylogenies from Multi-region Sequencing

Zheng Hu1,2 and Christina Curtis1,2,*

1Departments of Medicine and Genetics

2Stanford Cancer Institute

Stanford University School of Medicine, Stanford, CA 94305, USA

*Correspondence: cncurtis@stanford.edu


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