Biology subjects

Rotkevich, M.

Publications and source records attributed to Rotkevich, M..

3 recordsLinked to original sources

bioRxiv2026

Retinal resuscitation in post-mortem eyes

Vision loss compromises the quality of life of millions of people worldwide. Currently, vision-restoring therapies are lacking. Post-mortem preservation of human eyes may enable whole eye transplantation (WET) or therapeutic development. We developed an approach to cannulate the ophthalmic artery and perfuse post-mortem pig and human eyes using a custom-built device, Eye-in-Care-Box (ECaBox). Retinal vasculature imaging and reconstruction were used to assess perfusion efficacy using a supervised deep learning model. Without intervention, the retina degrades post-mortem, whereas perfusion preserves retinal structure and cell viability for up to 24-hours. Eyes were perfused within 30 minutes post-extraction, and regained light-responses persisted for up to 10 hours after death, challenging the notion that response to light ends at death. Our findings show that intact eyes can be resuscitated and preserved outside the body, supporting the ECaBox platform for WET preservation and pre-clinical therapeutic testing. Ultimately, ECaBox may bring vision-restoring treatments to patients.

neuroscience↗

bioRxiv2023

Graphlet-based hyperbolic embeddings capture evolutionary dynamics in genetic networks

MotivationSpatial Analysis of Functional Enrichment (SAFE) is a popular tool for biologists to investigate the functional organisation of biological networks via highly intuitive 2D functional maps. To create these maps, SAFE uses Spring embedding to project a given network into a 2D space in which nodes connected in the network are near each other in space. However, many biological networks are scale-free, containing highly connected hub nodes. Because Spring embedding fails to separate hub nodes, it provides uninformative embeddings that resemble a "hairball". In addition, Spring embedding only captures direct node connectivity in the network and does not consider higher-order node wiring patterns, which are best captured by graphlets, small, connected, non-isomorphic, induced subgraphs. The scale-free structure of biological networks is hypothesised to stem from an underlying low-dimensional hyperbolic geometry, which novel hyperbolic embedding methods try to uncover. These include coalescent embedding, which projects a network onto a 2D disk. ResultsTo better capture the functional organisation of scale-free biological networks, whilst also going beyond simple direct connectivity patterns, we introduce Graphlet Coalescent (GraCoal) embedding, which embeds nodes nearby on a hyperbolic disk if they tend to touch a given graphlet together. We use GraCoal embedding to extend SAFE. Through SAFE-enabled enrichment analysis, we show that GraCoal embeddings captures the functional organisation of the genetic interaction networks of fruit fly, budding yeast, fission yeast and E. coli better than graphlet-based Spring embedding. We show that depending on the underlying graphlet, GraCoal embeddings capture different topology-function relationships. We show that triangle-based GraCoal embedding captures functional redundancy between paralogous genes. Availabilityhttps://gitlab.bsc.es/dtello/graphlet-based-SAFE Contactnatasha@bsc.as Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2018

Genome-wide analysis of drug resistant Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in Russia

Mycobacterium tuberculosis is a highly studied pathogen due to public health importance. Despite progress in M.tuberculosis genome diversity analysis there remain insufficient data on genome analysis of M.tuberculosis strains associated with pulmonary vs. extrapulmonary TB (PTB or XPTB respectively) tissue localization. Here we conduct comparative analysis of whole-genome sequence (WGS) for clinical M.tuberculosis strains collected from patients with PTB (n=72) and XPTB (n=73) localization. We further analyze the incidence of point mutations widely used for drug resistance detection in laboratory practice.\n\nM.tuberculosis isolates were collected from patients with varying clinical status from 2007 to 2014 in Russia. Bacterial DNA was extracted and sequenced using MiSeq platform (Illumina).\n\nWGS data allowed identifying M.tuberculosis substrains associated with distinctions in the occurrence in PTB v s. XPTB cases. There occurred little statistically significant specific DNA variants or genotypes diagnostic of tissue distribution, however phylogenetic analyses did reveal M.tuberculosis genetic substrains associated with TB localization. XPTB was associated with Beijing CAO, A and 4.8 groups, while PTB localization was associated with group LAM (4.3). Further, XPTB strain in some cases showed elevated drug resistance patterns relative to PTB isolates. HIV is significantly associated with the development of XPTB in the Beijing B0/W148 group and among unclustered Beijing isolates.\n\nThis research analysis pinpointed genomic markers identified in XPTB and PTB with detailed characterization of drug-resistance markers of Russian M.tuberculosis isolates. We suggest that further comprehensive analysis of bacterial and human biological signatures might allow for better understanding consistent pattern of XPTB development.\n\nSummaryThis paper gives genome-wide characteristics of Mycobacterium tuberculosis strains collected from pulmonary and extrapulmonary tuberculosis patients:\n\n- M.tuberculosis genetic strains associated with TB tissue localization,\n\n- influence of HIV co-infection on TB dissemination;\n\n- mutations associated with M.tuberculosis drug resistance.

genomics↗