Biology subjects

Popov, R.

Publications and source records attributed to Popov, R..

5 recordsLinked to original sources

bioRxiv2026

Dual-Layer Serological Encoding: Integrating Pathogen-Derived and Host-Reactive Peptide Signatures Reveals Complementary Dimensions of HIV Immune Response

Serological diagnostics traditionally rely on pathogen-derived antigens to detect infection-specific antibody responses. Chronic infections also induce systemic immune remodeling that may be reflected in global antibody reactivity patterns beyond antigen specificity. Here we evaluate a dual-layer serological framework combining HIV-derived peptides with a host-derived peptide library designed to capture distributed antibody reactivity patterns. Using strict nested cross-validation in a cohort of 105 individuals, pathogen-derived 12-mer peptides achieved high classification performance with an AUC of 0.891, whereas the 10-mer host-based peptide library alone yielded moderate but statistically significant discrimination with an AUC of 0.805. Integration via regularized stacking resulted in only a modest additive improvement, reaching an AUC of 0.897, indicating partial redundancy in diagnostic ranking. In contrast, entropy and inequality analyses revealed substantial immune repertoire restructuring in HIV-positive individuals, characterized by reduced Shannon entropy and significant correlations between classifier probability and repertoire concentration. These findings support a dual-layer model of serology in which the integration of pathogen-derived and host-derived peptides into a meta model encode antigen specificity, whereas host-reactive signatures reflect systemic immune topology. Distinguishing diagnostic ranking from immune-state encoding provides a conceptual framework for multi-layer serological diagnostics.

immunology↗

bioRxiv2026

High-density peptide arrays detect tuberculosis through immune remodeling, not only antigen recognition alone

Serological diagnostics for tuberculosis rely on pathogen-derived antigens to detect infection-specific antibodies. Whether chronic TB infection also reshapes the global topology of the antibody repertoire remains largely unexplored. Here we profile serum antibody binding across 6,936 peptides in 105 individuals from three countries using two complementary libraries: Mycobacterium tuberculosis peptides (TBC) and a resemblance-ranking library representing the human self-proteome (RRL). We construct a five-dimensional immune state vector from distributional binding properties and map individual sera into an immune phase space. A remodeling classifier achieves virtually identical performance on pathogen-derived and host-derived peptides (AUC 0.63-0.73), demonstrating that the diagnostic signal arises from global repertoire restructuring rather than antigen-specific recognition. HIV co-infection partially masks this signal; restricting analysis to HIV-negative individuals increases AUC to 0.73 (permutation p = 0.005) and enables detection of smear-negative TB (AUC = 0.83, specificity 0.95 with three peptides). Phase-space projections reveal that TB severity maps onto a continuous remodeling gradient, with smear-negative patients occupying intermediate positions between healthy controls and smear-positive cases. These findings position high-density peptide arrays as sensors of antibody repertoire topology, enabling detection of chronic immune states beyond antigen-specific recognition.

immunology↗

bioRxiv2020

Substitutional landscape of a split fluorescent protein fragment

Split fluorescent proteins have wide applicability as biosensors for protein-protein interactions, genetically encoded tags for protein detection and localization, as well as fusion partners in super-resolution microscopy. We have established and validated a novel platform for functional analysis of leave-one-out split fluorescent proteins (LOO-FPs) in high throughput and with rapid turnover. We have screened more than 12,000 strand 10 variants using high-density peptide microarrays for binding and functional complementation in Green Fluorescent Protein. We studied the effect of peptide length and the effect of different linkers to the solid support and mapped the effect of all possible amino acid substitutions on each position as well as in the context of some single and double amino acid substitutions. As all peptides were tested in 12 duplicates, the analysis rests on a firm statistical basis allowing determination of robustness and precision of the method. We showed that the microarray fluorescence correlated with the affinity in solution between the LOO-FP and peptides. A double substitution yielded a peptide with 9-fold higher affinity than the starting peptide.

synthetic biology↗

bioRxiv2018

Whole-genome sequencing of three native cattle breeds originating from the northernmost cattle farming regions

Northern Fennoscandia and the Sakha Republic in the Russian Federation represent the northernmost regions on Earth where cattle farming has been traditionally practiced. In this study, we performed whole-genome resequencing to genetically characterize three rare native breeds Eastern Finncattle, Western Finncattle and Yakutian cattle adapted to these northern Eurasian regions. We examined the demographic history, genetic diversity and unfolded loci under natural or artificial selection. On average, we achieved 13.01-fold genome coverage after mapping the sequencing reads on the bovine reference genome (UMD 3.1) and detected a total of 17.45 million single nucleotide polymorphisms (SNPs) and 1.95 million insertions-deletions (indels). We observed that the ancestral species (Bos primigenius) of Eurasian taurine cattle experienced two notable prehistorical declines in effective population size associated with dramatic climate changes. The modern Yakutian cattle exhibited a higher level of within-population variation in terms of number of SNPs and nucleotide diversity than the contemporary European taurine breeds. This result is in contrast to the results of marker-based cattle breed diversity studies, indicating assortment bias in previous analyses. Our results suggest that the effective population size of the ancestral Asiatic taurine cattle may have been higher than that of the European cattle. Alternatively, our findings could indicate the hybrid origins of the Yakutian cattle ancestries and possibly the lack of intensive artificial selection. We identified a number of genomic regions under selection that may have contributed to the adaptation to the northern and subarctic environments, including genes involved in disease resistance, sensory perception, cold adaptation and growth. By characterizing the native breeds, we were able to obtain new information on cattle genomes and on the value of the adapted breeds for the conservation of cattle genetic resources.

genomics↗

bioRxiv2018

Whole blood transcriptome analysis reveals footprints of cattle adaptation to sub-arctic conditions

Indigenous cattle breeds in northern Eurasia have adapted to harsh climate conditions. The local breeds are important genetic resources with cultural and historical heritages, and therefore, their preservation and genetic characterization are important. In this study, we aim to identify genes and biological processes that are important for their adaptation to the cold and harsh conditions. For this purpose, we profiled the whole-blood transcriptome of two native breeds and one commercial breed using high-throughput RNA sequencing. More than 15,000 genes were identified, of which 2, 89, and 162 genes were significantly upregulated exclusively in Northern Finncattle, Yakutian cattle and Holstein cattle, respectively. The functional classification of these significantly differentially expressed genes identified several biological processes and pathways related to signalling mechanisms, cell differentiation, and host-pathogen interactions that, in general, point towards immunity and disease resistance mechanisms. The gene expression pattern observed in Northern Finncattle was more similar to that of Yakutian cattle, despite sharing similar living conditions as the Holstein cattle included in our study. In conclusion, our study identified unique biological processes in these breeds that help them to adapt and survive in sub-arctic environments.

genetics↗