AlignmentViewer: Sequence Analysis of Large Protein Families

Reguant, Roc; Antipin, Yevgeniy; Sheridan, Rob; Dallago, Christian; Diamantoukos, Drew; Luna, Augustin; Sander, Chris; Gauthier, Nicholas Paul

doi:10.12688/f1000research.22242.1

Cited by 5 publications

(5 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phylogenetic tree and sequence space. An orthogonal approach to tree inference is a multidimensional alignment embedding in sequence space (40), which confirms the unique evolutionary history for the superfamily, not readily seen in a tree graph (Fig. 2).…”

Section: Resultsmentioning

confidence: 66%

See 1 more Smart Citation

Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion

Neches

Kyrpides

Ouzounis

2021

mBio

View full text Add to dashboard Cite

Orf8, one of the most puzzling genes in the SARS lineage of coronaviruses, marks a unique and striking difference in genome organization between SARS-CoV-2 and SARS-CoV-1. Here, using sequence comparisons, we unequivocally reveal the distant sequence similarities between SARS-CoV-2 Orf8 with its SARS-CoV-1 counterparts and the X4-like genes of coronaviruses, including its highly divergent “paralog” gene Orf7a, whose product is a potential immune antagonist of known structure. Supervised sequence space walks unravel identity levels that drop below 10% and yet exhibit subtle conservation patterns in this novel superfamily, characterized by an immunoglobulin-like beta sandwich topology. We document the high accuracy of the sequence space walk process in detail and characterize the subgroups of the superfamily in sequence space by systematic annotation of gene and taxon groups. While SARS-CoV-1 Orf7a and Orf8 genes are most similar to bat virus sequences, their SARS-CoV-2 counterparts are closer to pangolin virus homologs, reflecting the fine structure of conservation patterns within the SARS-CoV-2 genomes. The divergence between Orf7a and Orf8 is exceptionally idiosyncratic, since Orf7a is more constrained, whereas Orf8 is subject to rampant change, a peculiar feature that may be related to hitherto-unknown viral infection strategies. Despite their common origin, the Orf7a and Orf8 protein families exhibit different modes of evolutionary trajectories within the coronavirus lineage, which might be partly attributable to their complex interactions with the mammalian host cell, reflected by a multitude of functional associations of Orf8 in SARS-CoV-2 compared to a very small number of interactions discovered for Orf7a. IMPORTANCE Orf8 is one of the most puzzling genes in the SARS lineage of coronaviruses, including SARS-CoV-2. Using sophisticated sequence comparisons, we confirm its origins from Orf7a, another gene in the lineage that appears as more conserved, compared to Orf8. Orf7a is a potential immune antagonist of known structure, while a deletion of Orf8 was shown to decrease the severity of the infection in a cohort study. The subtle sequence similarities imply that Orf8 has the same immunoglobulin-like fold as Orf7a, confirmed by structure determination. We characterize the subgroups of this superfamily and demonstrate the highly idiosyncratic divergence patterns during the evolution of the virus.

show abstract

Section: Resultsmentioning

confidence: 66%

“…S1a) and the latter (see Fig. S1b), respectively; these cross-similarity patterns were generated by AlignmentViewer (40). (Note that in this study, for data annotation purposes only, SARS-CoV-1 and SARS-CoV-2 are marked as "SARS-1" and "SARS-2," respectively.)…”

Section: Methodsmentioning

confidence: 99%

Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion

Neches

Kyrpides

Ouzounis

2021

mBio

View full text Add to dashboard Cite

show abstract

“…To check whether the original alignment can be consistently generated, it was split into two groups (494 M protein and 221 Orf3a sequence entries) and submitted to profile-profile matching with MAFFT [50] , that also identifies the same conserved regions. Cross-family similarities were computed with AlignmentViewer [51] and dimensionality reduction was aided by UMAP [52] as implemented in AlignmentViewer. Color-coding for sequence glyphs was selected according to MView [53] , using a residue width and height of 1 pixel.…”

Section: Methodsmentioning

confidence: 99%

A recent origin of Orf3a from M protein across the coronavirus lineage arising by sharp divergence

Ouzounis

2020

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

show abstract

“…The gap extend costs were set to one tenth of the gap open costs. The output alignments were analysed for hydropathy using the client-based tool AlignmentViewer (https://alignmentviewer.org/, 01.02.2023) [48].…”

Section: Methodsmentioning

confidence: 99%

Constructing networks for comparison of collagen types

Wesp,

Scholz,

Ziermann-Canabarro

et al. 2023

Preprint

View full text Add to dashboard Cite

Collagens are structural proteins that are predominantly found in the extracellular matrix, where they are mainly responsible for the stability and structural integrity of various tissues. There are several different types of collagens, some of which differ significantly in form, function, and tissue specificity. Subdivisions into so-called collagen families exist, which are defined on the basis of mainly clinical research. Collagens contain polypeptide strands (ɑ-chains). Their sequences are often analysed in view of clinical aspects, but problems arise with highly homologous sequence segments. To increase the accuracy of collagen classification and prediction of their functions, the structure of these collagens and their expression in different tissues could result in a better focus on sequence segments of interest. Here, we analyse collagen families with different levels of conservation. As a result, families with strong interchain hydrogen bonds can be found, such as fibrillar collagens, network-forming collagens, and FACITs. Moreover, collagen IV α-chains form their own cluster, and other collagen α-chains do not bond at all.

show abstract

AlignmentViewer: Sequence Analysis of Large Protein Families

Cited by 5 publications

References 10 publications

Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion

Atypical Divergence of SARS-CoV-2 Orf8 from Orf7a within the Coronavirus Lineage Suggests Potential Stealthy Viral Strategies in Immune Evasion

A recent origin of Orf3a from M protein across the coronavirus lineage arising by sharp divergence

Constructing networks for comparison of collagen types

Contact Info

Product

Resources

About