D-graph clusters flaviviruses and β-coronaviruses according to their hosts, disease type and human cell receptors

Abstract

Motivation: There is a need for rapid and easy to use, alignment free methods to cluster large groups of protein sequence data. Commonly used phylogenetic trees based on alignments can be used to visualize only a limited number of protein sequences. DGraph, introduced here, is a dynamic programming application developed to generate 2D-maps based on similarity scores for sequences. The program automatically calculates and graphically displays property distance (PD) scores based on physico-chemical property (PCP) similarities from an unaligned list of FASTA files. Such PD-graphs show the interrelatedness of the sequences, whereby clusters can reveal deeper connectivities. Results: PD-Graphs generated for flavivirus (FV), enterovirus (EV), and coronavirus (CoV) sequences from complete polyproteins or individual proteins are consistent with biological data on vector types, hosts, cellular receptors and disease phenotypes. PD-graphs separate the tick- from the mosquito-borne FV, clusters viruses that infect bats, camels, seabirds and humans separately and the clusters correlate with disease phenotype. The PD method segregates the β-CoV spike proteins of SARS, SARS-CoV-2, and MERS sequences from other human pathogenic CoV, with clustering consistent with cellular receptor usage. The graphs also suggest evolutionary relationships that may be difficult to determine with conventional bootstrapping methods that require postulating an ancestral sequence.

Synthetic proteins for COVID-19 diagnostics

“…Cross-over of the human virus into other species could also lead to changes in its infectivity severity, and resistance to therapies [ 68 , 70 ]. Variants or recombinants of these pathogens in animals could result in a virus that combines the high aerosol transmissibility of SARS-CoV-2 [ 7 , 71 , 72 ] with the high mortality in humans of SARS-CoV-1 or MERS [ 15 ]. Antigen based assays can be particularly useful in estimating the prevalence of COVID-19 infection in animals that may not show obvious illness, such as minks [ 68 ] or domestic cats [ 69 ].…”

“…S1) and length (1255/1277 aa for SARS/SARS-CoV2) [ 4 , 11 ]. Both of these viruses enter cells using the human ACE2 receptor [ 14 ], distinguishing them from other human pathogenic β-coronaviruses [ 15 ]. They also share some epitopes recognized by neutralizing antibodies isolated from survivors [ 1 , 16 ].…”

Synthetic protein antigens for COVID-19 diagnostics

“…SARS-CoV-2 has continued to mutate during its path through humanity, accumulating changes in this furin site and the RBD that may eventually affect its phenotype, immune sensitivity and resistance to therapies 4,[20][21][22][23] . Although both SARS viruses are quite distinct in sequence from the even deadlier β-CoV that causes MERS 24 , variants or recombinants of these pathogens could result in a virus that combines the high transmissibility of SARS-CoV-2 with the high mortality of SARS-CoV-1 or MERS. In addition, while the origins of both SARS viruses are unclear, there is a high probability that similar viruses are circulating, re-combining and mutating in some animal reservoir.…”