ArticlePLoS genetics2019
Paralog buffering contributes to the variable essentiality of genes in cancer cell lines.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Review and meta-analysis of the genetic Minimal Cut Set approach for gene essentiality prediction in cancer metabolism.Briefings in bioinformatics · 2024Pooled it
- Combined EP300 and CREBBP Expression Levels Regulate Human Trophoblast Differentiation.International journal of molecular sciences · 2026Article
- Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.Genome biology · 2025Article
- Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.Molecular systems biology · 2025Article
- Single-cell imaging of protein dynamics of paralogs reveals sources of gene retention.iScience · 2025Article
- Z-scores outperform similar methods for analyzing CRISPR paralog synthetic lethality screens.Genome biology · 2025Article
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.Nature genetics · 2025Article
- Evaluating sequence and structural similarity metrics for predicting shared paralog functions.NAR genomics and bioinformatics · 2025Article
- Incomplete paralog compensation generates selective dependency on TRA2A in cancer.PLoS genetics · 2025Article
- Ribosomal protein paralogues in ribosome specialization.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The theory of massively repeated evolution and full identifications of cancer-driving nucleotides (CDNs).eLife · 2024Article
- START domains generate paralog-specific regulons from a single network architecture.Nature communications · 2024Article
- Optimal methods for analyzing targeted pairwise knockout screens.bioRxiv : the preprint server for biology · 2024Article
- Frequent loss ofiScience · 2024Article
- What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?Pflugers Archiv : European journal of physiology · 2024Review
- Functional genomics in inborn errors of immunity.Immunological reviews · 2024Review
- Paralog dispensability shapes homozygous deletion patterns in tumor genomes.Molecular systems biology · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
What makes a gene essential for cellular survival? In model organisms, such as budding yeast, systematic gene deletion studies have revealed that paralog genes are less likely to be essential than singleton genes and that this can partially be attributed to the ability of paralogs to buffer each other's loss. However, the essentiality of a gene is not a fixed property and can vary significantly across different genetic backgrounds. It is unclear to what extent paralogs contribute to this variation, as most studies have analyzed genes identified as essential in a single genetic background. Here, using gene essentiality profiles of 558 genetically heterogeneous tumor cell lines, we analyze the contribution of paralogy to variable essentiality. We find that, compared to singleton genes, paralogs are less frequently essential and that this is more evident when considering genes with multiple paralogs or with highly sequence-similar paralogs. In addition, we find that paralogs derived from whole genome duplication exhibit more variable essentiality than those derived from small-scale duplications. We provide evidence that in 13-17% of cases the variable essentiality of paralogs can be attributed to buffering relationships between paralog pairs, as evidenced by synthetic lethality. Paralog pairs derived from whole genome duplication and pairs that function in protein complexes are significantly more likely to display such synthetic lethal relationships. Overall we find that many of the observations made using a single strain of budding yeast can be extended to understand patterns of essentiality in genetically heterogeneous cancer cell lines.
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