Biology subjects

Mombach, D. M.

Publications and source records attributed to Mombach, D. M..

3 recordsLinked to original sources

bioRxiv2026

TEscape: Defining the human transposable element transcriptome using multiplatform long-read sequencing

Transposable elements (TEs) not only account for half of the human genome sequence but also generate transcripts that contribute to transcriptomic diversity. Yet, their repetitive nature has hindered accurate quantification of the full TE-derived transcriptome, a challenge that long-read sequencing can overcome. Here, we combined multiplexed arrays isoform sequencing (MAS-ISO-seq) with a dedicated computational framework (TEscape) to perform an in-depth annotation of the human TE transcriptome. To capture the breadth of human transcriptome diversity, we profiled six representative cell types spanning three distinct biological contexts, including metabolism with, primary patient-derived adipogenic cells at two differentiation stages, and iPSC derived hepatic progenitor cells; the nervous system with iPSC-derived neurons, neural progenitor cells (NPCs), and pluripotency using induced pluripotent stem cells (iPSCs). Together, these datasets yielded over 235 million full-length long reads. First, to assess data coverage and transcriptome depth, we quantified protein-coding gene expression, detecting 14,312 genes (73.6% of all annotated protein-coding genes), which is a level consistent with deep and comprehensive transcriptome representation. Second, focusing on TE-derived transcripts, we identified >83,000 previously unannotated isoforms, the vast majority (84%) originating from a complex combination of multi-TEs. We also identified solo TEs, which are predominantly from LINE1 (14%). We confirmed that TE-transcripts are able to be exemplified by signatures detected in Liver Hepatocellular Carcinoma (LICH). Together, MAS-ISO-seq and TEscape establish the first long-read-based, high-resolution atlas of transcribed human TEs, providing a foundational resource for integrative transcriptome analyses and for investigating TE expression and regulation in health and disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/737305v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@18158aeorg.highwire.dtl.DTLVardef@e51fdforg.highwire.dtl.DTLVardef@8f9504org.highwire.dtl.DTLVardef@804113_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract C_FIG

bioinformatics↗

bioRxiv2026

Processed pseudogenes as dynamic substrates of vertebrate genome evolution

Pseudogenes, gene copies presumed nonfunctional, are widespread products of genome evolution, yet their retention under selection and functional significance across vertebrate diversity remain poorly understood. Here, by analyzing 244 high-quality, chromosome-scale genomes from the Vertebrate Genomes Project spanning seven major vertebrate lineages, we show that the most abundant class of pseudogenes, processed pseudogenes (retrocopies), is a dynamic substrate for evolutionary innovation rather than an inert relic. Retrocopy abundance varies by more than an order of magnitude across lineages, closely tracks autonomous retrotransposon content, and a considerable fraction retains intact open reading frames under purifying selection. We establish a two-stage model in which a conserved formation bias toward highly expressed housekeeping genes is followed by lineage-specific selective filtering that shapes distinct functional repertoires. Testing this model, we show that the mammalian X chromosome exports retrocopies to autosomes at significantly elevated rates enriched for functionally constrained copies, establishing meiotic sex chromosome inactivation as the selective driver. Furthermore, tumor suppressor gene retrocopies accumulate preferentially over oncogene retrocopies in large-bodied and long-lived mammalian lineages, identifying retrocopy-mediated tumor suppressor dosage expansion as a previously unrecognized genomic correlate of Petos paradox. Beyond cancer-related dynamics, retrocopy abundance itself correlates with key mammalian life-history traits, including brain mass, generation length, and reproductive timing, which suggests that retrocopy turnover is broadly coupled to organismal pace-of-life. These findings recast retrocopies as a major axis of vertebrate genome evolution and provide a comprehensive resource for studying gene duplicate innovation.

genomics↗

bioRxiv2023

TRANSPOSABLE ELEMENTS ALTER GENE EXPRESSION AND MAY IMPACT RESPONSE TO CISPLATIN THERAPY IN OVARIAN CANCER

Cisplatin is widely employed for cancer treatment; therefore, understanding resistance to this drug is critical for therapeutic practice. While studies have delved into differential gene expression in the context of cisplatin resistance, findings remain somewhat scant. In this study, we employed RNA-seq, ATAC-seq, and in-depth bioinformatics analyses to perform a detailed investigation of the cellular transcriptome, centering on Transposable Elements (TEs) expression in ovarian cancer cell lines both sensitive and resistant to cisplatin treatment. Our results reveal that cisplatin therapy alters the expression of protein-coding genes, but also key TEs, including LINE1, Alu, and endogenous retroviruses, in both cisplatin-sensitive and -resistant cell lines. By co-expressing with downstream genes or by creating chimeric transcripts with host genes at their insertion sites, these TEs seem to control the expression of protein-coding genes, including tumor-related genes. Notably, our model uncovers TEs influencing the expression of cancer genes and cancer pathways. Collectively, our findings indicate that TEs alterations associated with cisplatin treatment occur in critical cancer genes and cellular pathways synergically. In conclusion, this research highlights the importance of considering the entire spectrum of transcribed elements in the genome, especially TE expression, for a complete understanding of complex models like cancer response to treatment.

cancer biology↗