Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features

Lassmann, Timo; Frings, Oliver; Sonnhammer, Erik L. L.

doi:10.1093/nar/gkn1006

Cited by 255 publications

(208 citation statements)

References 33 publications

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“…We also manually merged neighbor contigs in the Velvet assemblies exhibiting a 10-to 90-nucleotide overlap with each other. For each sample, a multiple alignment comprising the GK18 reference sequence, the Velvet assembly, and the MIRA assembly was performed using Kalign2 (23). To generate the final sequences, conserved regions between the Velvet and MIRA assemblies were accepted, and the discrepancies were manually corrected by comparing the original read alignments to input sequences.…”

Section: Methodsmentioning

confidence: 99%

Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity

Olp

Jeanniard

Marimo

et al. 2015

J Virol

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Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries-where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap since it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment protocol followed by Illumina deep-sequencing, we generated and analyzed 16 unique Zambian, KS-derived, KSHV genomes. We enriched KSHV DNA over cellular DNA 1,851 to 18,235-fold. Enrichment provided coverage levels up to 24,740-fold; therefore, supporting highly confident polymorphism analysis. Multiple alignment of the 16 newly sequenced KSHV genomes showed low level variability across the entire central conserved region. This variability resulted in distinct phylogenetic clustering between Zambian KSHV genomic sequences and those derived from Western countries. Importantly, the phylogenetic segregation of Zambian from Western sequences occurred irrespective of inclusion of the highly variable genes K1 and K15. We also show that four genes within the more conserved region of the KSHV genome contained polymorphisms that partially, but not fully, contributed to the unique Zambian KSHV whole-genome phylogenetic structure. Taken together, our data suggest that the whole KSHV genome should be taken into consideration for accurate viral characterization. IMPORTANCEOur results represent the largest number of KSHV whole-genomic sequences published to date and the first time that multiple genomes have been sequenced from sub-Saharan Africa, a geographic area where KS is highly endemic. Based on our new sequence data, it is apparent that whole-genome KSHV diversity is greater than previously appreciated and differential phylogenetic clustering exists between viral genomes of Zambia and Western countries. Furthermore, individual genes may be insufficient for KSHV genetic characterization. Continued investigation of the KSHV genetic landscape is necessary in order to effectively understand the role of viral evolution and sequence diversity on KSHV gene functions and pathogenesis. K aposi's sarcoma-associated herpesvirus (KSHV), or human herpesvirus 8 (HHV-8), is the etiologic agent for all forms of Kaposi's sarcoma (KS) (1). KS manifests as an endothelial tumor primarily on the skin but can also involve mucosal membranes and visceral organs. Among the HIV-uninfected population, KS is rare worldwide; however, HIV infection and immunosuppression greatly increase the risk of developing KS (2). In sub-Saharan Africa, HIV is epidemic, and KSHV is endemic. Accordingly, KS is one of the most common cancers in sub-Saharan A...

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Section: Methodsmentioning

confidence: 99%

Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity

Olp

Jeanniard

Marimo

et al. 2015

J Virol

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“…Structural alignments were performed using MUSTANG (33), and the structures were rendered using PYMOL (http:// www.pymol.org/) and SWISS-PDBviewer (http://spdbv.vital-it.ch/). Ligandbinding residues were determined using a custom script that searches for atoms within spheres of specified radius, such as 3.0 Å or 5.0 Å. Entropy calculations were performed with a custom script using the alignments generated by KALIGN (34). The entropy was calculated using the Shannon entropy formula: H ¼ − ∑ M i¼1 P i log z P i , where P i is the fraction of a given amino acid i, and M the total number of different amino acids.…”

Section: Methodsmentioning

confidence: 99%

A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

Deng

Velikovsky

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Adaptive immunity in jawless vertebrates is mediated by leucine-rich repeat proteins called "variable lymphocyte receptors" (VLRs). Two types of VLR (A and B) are expressed by mutually exclusive lymphocyte populations in lamprey. VLRB lymphocytes resemble the B cells of jawed vertebrates; VLRA lymphocytes are similar to T cells. We determined the structure of a high-affinity VLRA isolated from lamprey immunized with hen egg white lysozyme (HEL) in unbound and antigen-bound forms. The VLRA-HEL complex demonstrates that certain VLRAs, like γδ T-cell receptors (TCRs) but unlike αβ TCRs, can recognize antigens directly, without a requirement for processing or antigen-presenting molecules. Thus, these VLRAs feature the nanomolar affinities of antibodies, the direct recognition of unprocessed antigens of both antibodies and γδ TCRs, and the exclusive expression on the lymphocyte surface that is unique to αβ and γδ TCRs.crystal structure | T-cell receptor | variable lymphocyte receptor | evolution | antigen binding

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“…Multiple alignments were created using Kalign at default settings, 40 except in the case of the multiple sequence alignment in Fig. 4 where a lower gap extension at 0.1 was used.…”

Section: Alignmentsmentioning

confidence: 99%

Nebulin: A Study of Protein Repeat Evolution

Björklund

Light

Sagit

et al. 2010

Journal of Molecular Biology

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Protein domain repeats are common in proteins that are central to the organization of a cell, in particular in eukaryotes. They are known to evolve through internal tandem duplications. However, the understanding of the underlying mechanisms is incomplete. To shed light on repeat expansion mechanisms, we have studied the evolution of the muscle protein Nebulin, a protein that contains a large number of actin-binding nebulin domains.Nebulin proteins have evolved from an invertebrate precursor containing two nebulin domains. Repeat regions have expanded through duplications of single domains, as well as duplications of a super repeat (SR) consisting of seven nebulins. We show that the SR has evolved independently into large regions in at least three instances: twice in the invertebrate Branchiostoma floridae and once in vertebrates.In-depth analysis reveals several recent tandem duplications in the Nebulin gene. The events involve both single-domain and multidomain SR units or several SR units. There are single events, but frequently the same unit is duplicated multiple times. For instance, an ancestor of human and chimpanzee underwent two tandem duplications. The duplication junction coincides with an Alu transposon, thus suggesting duplication through Alu-mediated homologous recombination.Duplications in the SR region consistently involve multiples of seven domains. However, the exact unit that is duplicated varies both between species and within species. Thus, multiple tandem duplications of the same motif did not create the large Nebulin protein.Finally, analysis of segmental duplications in the human genome reveals that duplications are more common in genes containing domain repeats than in those coding for nonrepeated proteins. In fact, segmental duplications are found three to six times more often in long repeated genes than expected by chance.

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Kalign2: high-performance multiple alignment of protein and nucleotide sequences allowing external features

Cited by 255 publications

References 33 publications

Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity

Whole-Genome Sequencing of Kaposi's Sarcoma-Associated Herpesvirus from Zambian Kaposi's Sarcoma Biopsy Specimens Reveals Unique Viral Diversity

A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey

Nebulin: A Study of Protein Repeat Evolution

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