Biology subjects

Vassetzky, Y. S.

Publications and source records attributed to Vassetzky, Y. S..

3 recordsLinked to original sources

bioRxiv2026

RNAseq analysis reveals the recurrent loss of heterozygosity in lung cancer and associated transcription patterns

A key limitation in cancer transcriptomics is the lack of accompanying genomic profiling such as whole-genome sequencing (WGS) or copy number alteration (CNA) data. Here we address this by showing that RNA-seq alone can be used to infer chromosomal aberrations and identify biologically meaningful patterns in lung cancer. Through a large-scale meta-analysis of publicly available RNA-seq datasets from non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and matched controls, we reconstructed large scale CNA profiles and identified deletions in 3p, 9p, and 17p as the most frequent genomic events. Validation against paired WGS data confirmed a high degree of accuracy for RNA-seq-based inference. Our analyses revealed that while deletion-associated transcriptional heterogeneity exists, approximately 25% of differentially expressed genes were shared across all three deletion classes, indicating a conserved oncogenic program in lung cancer. Enrichment analysis linked these shared genes to pathways governing cell division, DNA replication, and extracellular matrix organization, while deletion-specific effects reflected disruption of tumor suppressor pathways, notably p53 signaling in 17p-deleted tumors, leading to deregulation of NOS2 and PLOD2. Integrating gene-level expression data, we identified both shared and deletion-specific biomarkers: TPX2 was consistently overexpressed across all deletion groups, while PTPRZ1 and CLDN9 were uniquely associated with del3p and del9p, respectively. Experimental validation in lung cancer cell lines confirmed these predictions, particularly the upregulation of CLDN9 in del9p carriers. By demonstrating that RNA-seq data can capture large-scale chromosomal events and reveal their transcriptional consequences, this study establishes an efficient framework for genomic inference and biomarker discovery, introducing CLDN9 as a novel, deletion-specific marker with potential prognostic and therapeutic value for 9p-deleted lung cancers.

cancer biology↗

bioRxiv2021

Mechanisms and evolutionary implications of integration of different functions within HIV-1 Tat

During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses.

evolutionary biology↗

bioRxiv2020

Lung epithelial stem cells express SARS-CoV-2 entry factors: implications for COVID-19

SARS-CoV-2 can infiltrate the lower respiratory tract, resulting in severe respiratory failure and a high death rate. Normally, the airway and alveolar epithelium can be rapidly reconstituted by multipotent stem cells after episodes of infection. Here, we analyzed published RNA-seq datasets and demonstrated that cells of four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including Ace2. Thus, stem cells can be potentially infected by SARS-CoV-2, which may lead to defects in regeneration capacity partially accounting for the severity of SARS-CoV-2 infection and its consequences.

cell biology↗