Satellite information to the recently published papers

corresponding author: Jaroslav Kubrycht, National Institute of Public Health, Prague, Czech Republic, e-mail address: jkub@.post.cz

item name: P2006
paper: Ancient Phylogenetic Beginnings of Immunoglobulin Hypermutation
authors: Kubrycht J., Sigler K., Ruzicka M., Soucek P., Borecky J., Jezek P.
published in: Journal of Molecular Evolution, 63(5) 691-706

abstract:
Many structures and molecules closely related to that involved in the specific process of immunoglobulin (Ig) hypermutation existed before the appearance of primordial Ig genes. Consequently, these structures can be found even in animals and organisms distinct from vertebrates; likewise, homologues of hypermutation enzymes are present in broad range of species from bacteria to mammals. Our analysis, based predominantly on primary structure, demonstrates the existence of molecules similar to Ig domains, variable Ig domains (IGv) and antigen receptors (AR) in unicellular organisms, non-vertebrate metazoans and non-vertebrate Coelomata, respectively. In addition, we deal here with some important structural properties of CDR1-like segments of the selected sponge adhesion molecule GCSAMS exhibiting chimerical Ig domain similarities, and demonstrate occurrence of conserved regions corresponding to Ohno´s modern intact primordial building block in C-terminal part of IGv-related segments of non-vertebrate origin. The results of our analysis are also discussed with respect to possible phylogeny of molecules preceding hypothetical common AR ancestor.

(i) web page supplement (please click here)
(ii) additional comments and illustrations
overview (pdf)
schemes (ppt)

item name: P2014
paper: Sequence-based prediction of linear autoepitopes involved in pathogenesis of IPAH and the corresponding organism sources of molecular mimicry
authors: Kubrycht J., Novotna J.
published in: International Journal of Bioinformatics Research and Applications, 10(6) 587-617 2014

abstract:
We proposed here a sequence-based approach predicting some microorganisms as possible sources of autoantigen-related molecular mimicry concerning Idiopathic Pulmonary Arterial Hypertension (IPAH) and related hypertension mostly accompanying autoimmune diseases and AIDS (APAH). This approach (SPECIES_VALENCE) processes the database occurrences of linear autoepitope-related short Dense Quasi-Pattern Sequences (DQPA) generated based on identities of important autoantigenic sequences. The corresponding enumeration comprises two types of statistical evaluations performed in each of eight proposed models. Based on this enumeration, we selected nine microorganisms, whereas revaluation of the obtained scoring values restricted Pseudomonas aeruginosa, Aspergillus fumigatus and the two co-infecting herpes viruses (Epstein Barr virus and cytomegalovirus) as most favourable. The results are discussed in terms of (a) the validity of increased DQPA occurrence in functionally correlated sequences, (b) the possible mechanisms leading to autoantibody response, (c) selected additional pathogenic effects of predicted microorganisms and (d) possible effects of cross-reactivities and immune tolerance.

web page supplement: (please click here)

item name: P2016
paper: Antibody-like phosphorylation sites in focus of statistically based bilingual approach
authors: Kubrycht J., Sigler K., Soucek P., Hudecek J.
published in: Computational Molecular Bioscience, 6(1) 1-22 2016

abstract:
In accordance with previous reports, the sequences related to phosporylated protein segments occur in conserved variable domains of immunoglobulins including first of all certain N-terminally located segments. Consequently, we look here for the sequences 1) composing human and mouse proteins different from antigen receptors, 2) identical with or highly similar to nucleotide sequence representatives of conserved variable immunoglobulin segments and 3) identical with or closely related to phosphorylation sites. More precisely, we searched for the corresponding actual pairs of DNA and protein sequence segments using five-step bilingual approach employing among others a) different types of BLAST searches, b) two in-principle-different machine-learning methods predicting phosphorylated sites and c) two large databases recording existing phosphorylation sites. The approach identified seven existing phosphorylation sites and thirty-seven related human and mouse segments achieving limits for several predictions or phylogenic parameters. Mostly serines phosporylated with ataxia-telangiectasia-related kinase (involved in regulation of DNA-double-strand-break repair) were indicated or predicted in this study. Hypermutation motifs, located in effective positions of the selected sequence segments, occurred significantly less frequently in transcribed than non-transcribed DNA strands suggesting thus the incidence of mutation events. In addition, marked differences between the numbers and proportions of human and mouse cancer-related sequence items were found in different steps of selection process. The possible role of hypermutation changes within the selected segments and the observed structural relationships are discussed here with respect to DNA damage, carcinogenesis, cancer vaccination, ageing and evolution. Taken together, our data represent additional and sometimes perhaps complementary information to the existing databases of empirically proven phosphorylation sites or pathogenically important spots.

web page supplements:
More detailed descriptions of employed procedures and supplementary comments (file SF1)
Dictionary of abbreviations (file SF2)
Supplementary illustrations to overall methodological scheme displayed in Figure 1 (file SF3)
Extractable tables with the selected segments and their properties
Erratum 1