A new version, Genomenal 2.11.0, has been released.

Key Changes

• Ancestry analysis has been added.
• A new report block titled “Interpretation of Genotypes in the SNP Panel” has been introduced. It enables genotyping and annotating selected polymorphisms from the dbSNP database.
• New polygenic trait prediction models have been added.
• The ClinVar database has been updated to the July 2025 release.

Useful Additions

• The ability to edit the interpretation of sections and genetic variants directly within the report.
• The ability to generate a report based on genetic variants that meet multiple combined filtering conditions. It makes easier setup of automated criteria for Preconception screening and other like reports.
• The TwistExome 2.0 exome panel (Twist Bioscience, USA) has been added.
• The Agilent SureSelect Human All Exon V8 reagent has been added.
• The variant genotype is now displayed in both allele and nucleotide notation.
• Exon entries now indicate the total number of exons in the transcript.

Improvements

• The genetic variants table in the report has been standardized.
• The loading speed of the SNV Viewer module has been optimized.

Employees of NOVEL contributed to the article "Transcriptomic Analysis of TDP1-Knockout HEK293A Cells Treated with a TDP1 Inhibitor (Usnic Acid Derivative)," published in the International Journal of Molecular Sciences.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a key enzyme for the repair of stalled topoisomerase 1 (TOP1)-DNA complexes. Previously, we obtained HEK293A cells with homozygous knockout of the TDP1 gene by the CRISPR/Cas9 method and used them as a cell model to study the mechanisms of anticancer therapy and to investigate the effect of TDP1 gene knockout on gene expression changes in the human HEK293A cell line by transcriptome analysis. In this study, we investigated the effect of a TDP1 inhibitor ((R,E)-2-acetyl-6-(2-(2-(4-bromobenzyliden) hydrazinyl) thiazol-4-yl)-3,7,9-trihydroxy-8,9b-dimethyldibenzo[b,d] furan-1(9bH)-one, OL9-119, an usnic acid derivative), capable of potentiating the antitumor effect of topotecan, as well as its combination with topotecan, on the transcriptome of wild-type and TDP1 knockout HEK293A cells. OL9-119 was found to be able to reduce cell motility by decreasing the expression of a number of genes, which may explain the antimetastatic effect of this compound. Differentially expressed genes (DEGs) related to electron transport, mitochondrial function, and protein folding were also identified under TDP1 inhibitor treatment.

The full text of the article can be found here: https://www.mdpi.com/1422-0067/26/19/9291

As part of the ONCOMARKERS-2025 conference, a hands-on training school on the NanoFor SPS sequencing platform was successfully conducted. The event took place at the Institute of Chemical Biology and Fundamental Medicine, SB RAS (Novosibirsk), and was organized with the support of:

• Syntol Research and Production Company LLC
• Novel Software Systems LLC 
• ICBFM SB RAS 

Program Highlights:

• Practical session on DNA extraction from blood samples and library preparation for BRCA1/BRCA2 genes.
• Equipment training:
  — COLIBRI 48 workstation,
  — Qubix fluorometer,
  — NanoFor 05 genetic analyzer,
  —  NanoFor SPS sequencer.
• Bioinformatics analysis using Genomenal software.

Participants gained comprehensive, hands-on experience encompassing the entire workflow — from DNA extraction to data interpretation. The acquired skills are valuable for both diagnostic applications in hereditary disease research and broader scientific studies.

We extend our sincere gratitude to the organizers and participants for their active engagement and productive collaboration!

We are pleased to announce the release of Genomenal 2.10.0, featuring significant improvements.

Key Enhancements:

• New Pharmacogenetics Report — Provides interpretation of patient genetic data to predict individual drug responses.
• Full Compatibility with whole-genome sequencing data from the Russian-made NanoFor SPS sequencer.
• Optimized VCF Output — SNVs/Indels are now annotated in a standard VCF format without additional annotation columns, reducing file size

The journal iScience has published the article “Mutational pressure promotes release of public CD8+ T cell epitopes by proteasome from SARS-CoV-2 RBD of Omicron and its current lineages”, co-authored by a NOVEL researcher.

This study demonstrates that mutations in the Omicron B.1.1.529 variant significantly enhance the release of two immunodominant HLA class I epitopes: 504-GHQPYRVVVL-513 and 496-SFRPTYGVGH-505. These epitopes are generated through the efficient processing—hydrolysis—of the receptor-binding domain (RBD) by both constitutive proteasomes (c20S) and immune proteasomes (i20S). These proteasomes break down the protein into antigenic fragments, which are then presented to the immune system to trigger a protective response.

The authors highlight the global significance of HLA haplotypes capable of presenting these epitopes. Key HLA molecules, such as HLA-B07:02, HLA-B08:01, HLA-B51:01, HLA-C01:02, HLA-C06:02, and HLA-C07:02, are widely distributed among populations and cover up to 82% and 27% of the global population for the 504-GHQPYRVVVL-513 and 496-SFRPTYGVGH-505 epitopes, respectively. This explains the decrease in COVID-19 mortality rates in regions with a high prevalence of these haplotypes after December 2021, when Omicron became the dominant and persistent strain.

The full text article is here https://www.cell.com/iscience/fulltext/S2589-0042(25)00133-6.

The paper «Enhancing the reverse transcriptase function in Taq polymerase via AI-driven multiparametric rational» is published in the journal of Frontiers in Bioengineering and Biotechnology. The result is based on the AI models developed in NOVEL and Institute of Artificial Intelligence MSU.

We trained a Ridge regression model to predict multiple enzyme properties in the wild type and mutated Taq polymerase. The model is based on the embeddings of Taq polymerase primary structure generated by a protein language model. Using the regression model we conducted an in silico screen of over 18 million potential mutations, narrowing the field to 16 top candidates for comprehensive wet-lab evaluation.

This approach led to the identification of 18 enzyme variants that exhibited markedly improved reverse transcriptase activity while maintaining a favorable balance of other key properties. Several enzymes validated via this procedure were effective in single-enzyme real-time reverse-transcription PCR setups, implying their utility for the development of new tools for real-time reverse-transcription PCR technologies, such as pathogen RNA detection and gene expression analysis.

Our approach offers a robust framework for designing enzyme mutants tailored to specific biotechnological applications. The full text article is here https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2024.1495267/full.

Main updates:

• Introducing CNV Viewer - Copy Number Variation analysis tool with filtering, sorting, and prioritizing, integrated with IGV and Decipher database, records pinning, user custom interpretation, pathogenicity and boundary refinement, hierarchical and flat full/split record view modes.
• The new homepage for easy analysis, interpretation, work step tracking.
• User notifications on completion of sample processing and batch analyses.

Key changes:

• Genomenal can now combine any number of samples into a single table (in VCF format), with unsequenced parts of the samples marked in a special way (with "./." genotype). This capability provides the basis for qualitative population analysis, variant frequency calculations and other population genetics tasks. The results of such analyses can be loaded into Genomenal as user annotations.
• A feature has been developed to merge images into a single image at the data loading stage.
• This is particularly relevant when sequencers produce multiple files for a single sample, spread across multiple lanes of the sequencer. It is also possible to combine heterogeneous data into a single sample.
• Population and panel analysis functionality for large numbers of samples has been introduced.
• RefSeq annotation has been introduced.
• Users can now analyze the effects of variants on both Ensembl and RefSeq transcripts. Easily select the annotation system you are familiar with.
• Grouping of filter fields in the query builder has been added to improve navigation and usability.
• Introduced the ability to resume interrupted sample downloads, making it easier to work with large amounts of data.
• If communication is interrupted, the sample download can almost always be resumed from the same location.
• The Variant Viewer tool now has the ability to display the "HGVSp long" column, allowing you to view the variant annotation in the format recommended by the International Human Genetic Variant Consortium.
• GRM has been improved with an interface to manage organization, add interpretation steps and notify other users of changes to steps. Working in a team is now even more convenient.

New features:

• A new, unique interpreter collaboration system - Genomic Relationship Management.
• A new pipeline has been introduced that allows for the prediction of polygenic traits for samples in FASTQ format.
• The display now includes the interpretation of identical variants in other samples that have been uploaded to the account and previously interpreted.
• A new setting, "Compound Heterozygotes", has been added to the query builder. This setting, used after applying other filters, allows for the extraction of those variants that may be in a compound heterozygous form from the filtered ones. This setting is particularly relevant for group analysis.
• The display now includes the interpretation of identical variants in other samples uploaded to the account and previously interpreted.
• The ability to add tracks of other samples uploaded to the account to the Integrative Genomics Viewer (IGV) has been implemented.

Improvements:

• Databases updated to the latest versions.
• Added support for variant phase groups (new column in VV "Phase group status", by default the column is not shown).
• Added Enigma database annotation (new columns in VV "ENIGMA clinical significance" and "ENIGMA clinical significance comment", by default the columns are not shown).
• Added new scorers MaxEntScan, MutationAssessor, added precalculated CADD and SpliceAI.
• Added ability to export variants whose parameters (interpretation, anchoring, pathogenicity, etc.) have been changed.
• Added a new "Label" column in the Variant Viewer (VV) to allow the significance of a variant to be marked or to indicate that a variant is a sequencing error (by default the column is not displayed).
• Added the ability to filter by multiple HPO terms.
• Added the ability to sort by multiple columns.
• Added additional external links to open databases (UCSC, Franklin).
• Added color coding of ClinVar pathogenicity, shortened pathogenicity names.
• Copying variant positions from the variant table to VV is now done with a single mouse click.
• In VV, a frequency filter (using gnomAD) with defined thresholds has been added to the basic filters. The option is enabled in the VV settings in the user profile.
• The ability to add new samples to a previously created run has been implemented.
• The Variant Interpretation/Comment field can now be edited in the General tab at the bottom of the VV window.
• Variant details can be opened in a separate tab for easier comparison and analysis by right clicking on the "Show Variant Details" icon in the variant row.
• Finding the required parameters to set filter conditions for variants in the Query Builder has been improved.

Employees of NOVEL collaborated in the publication of the article "RNAseq profiling of blood from patients with coronary artery disease: "Signature of a T cell imbalance" in the Journal of Molecular and Cellular Cardiology Plus.

The investigation of regulatory T cell dysfunction in CAD is the focus of the article. Researchers have accurately analyzed the biggest sample of gene activity in CAD using cutting-edge sequencing and bioinformatics methods.

It has been demonstrated that transcripts connected to the immunological synapse (interaction) are particularly connected to CAD. T-cells and B-cells can communicate with diverse antigen-presenting and immunomodulatory cells at the immunological synapse, which is contact-dependent. Fibromodulin (FMOD; upregulated 2.8-fold in CAD) is one of the most differentially expressed genes and is known to be associated with atherosclerosis, cardiomyopathy, and iron-dependent programmed cell death.

Moreover, transcripts for proteins connected to the immunological synapse's formation and operation have been found. Nebulette is involved in the binding of actin and desmin for the operation of the cytoskeleton and vesicular movement (increases 2.4 times in CAD). Transcripts that were directly connected to T cell activity and the regulation of differentiation were present in the immunological synapses' signaling pathways. T-cell activation is mediated by butyrophilin, which is elevated 1.7-fold in coronary artery disease.

The paper demonstrates how alternative sequencing technologies (SeqLL and Illumnina) enable the identification of transcripts linked to alterations in T regulatory cells, but with distinctly distinct transcripts linked to CAD.

The full text of the article can be found here: https://www.sciencedirect.com/science/article/pii/S277297612300003X?via%3Dihub