Base by Base

Peeters MKR et al., Proceedings of the National Academy of Sciences (PNAS) - A perspective outlining how genome doubling (polyploidy) reshapes genomes, phenotypes, and ecological interactions and how its immediate effects can be harnessed across agriculture, aquaculture, industrial biotechnology, and medicine to advance a sustainable bioeconomy. Key terms: polyploidy, bioeconomy, genetic diversity...

Sarabia Olivera L et al., PNAS - A perspective that surveys how diverse stresses trigger whole‑genome doubling (polyploidy) across fungi, plants, and animals, outlines common cell‑cycle mechanisms that produce polyploid cells, and evaluates the beneficial and detrimental consequences for genomes, cells, tissues, and applied contexts. Key terms: polyploidy, endocycles, oxidative stress, genome inst...

Haycocks JRJ et al., PNAS - This episode examines the discovery of CisR, a small RNA produced from the 3’UTR of prtV in Vibrio cholerae, which posttranscriptionally represses the CTXϕ-encoded cep mRNA via Hfq-mediated base-pairing. CisR accumulation is controlled by HapR and CRP and processed by RNase E, linking quorum sensing and carbon status to phage activation. We discuss the experimental evid...

Koprulu M et al., Cell - A 38-cohort proteogenomic meta-analysis of up to 78,664 people maps fine‑mapped protein quantitative trait loci (pQTLs) across 1,116 circulating proteins, uses machine learning to assign trans effector genes, and triangulates genetic and observational evidence to highlight disease mechanisms and therapeutic opportunities. Key terms: proteogenomics, protein QTLs, N-linked g...

Nagahata Y et al., PNAS - A transcriptome-driven reconstruction of blood cell evolution shows modern animal blood lineages arose by repurposing an ancestral unicellular toolkit. The study traces macrophage-like origins, a bilaterian mast/killer split, and later deuterostome/vertebrate innovations. Key terms: blood cell evolution, macrophage, mast cell, Fos, thymus. Study Highlights: The authors us...

Battistoni G et al., PNAS - This paper presents BALI, a light-driven method that writes combinatorial DNA spatial barcodes directly onto biomolecules in tissue by iterative photocleavage and ligation, enabling user-defined, scalable spatial profiling of RNA, chromatin accessibility, or both from the same section and automation via a LightScribe instrument. Key terms: spatial multiomics, photocaged...

Abadie FMC et al., Cell Genomics - Abadie et al. present prime‑SGE, a pooled prime‑editing framework that installs thousands of precise point mutations across multiple oncogenes and identifies drug‑resistance variants by sequencing integrated pegRNAs after positive‑selection with kinase inhibitors. The method resolved known resistance mutations (e.g., EGFR C797S, KRAS G12 variants), uncovered less...

Mortazavi M et al., Cell Genomics - PaperCast Base by Base discusses a long-read whole-genome sequencing study of 267 individuals from 63 families that increased detection of structural variants and tandem repeats, resolved complex rearrangements, linked repeat expansions to methylation at FMR1, and estimated rare-variant contributions to ASD heritability. Key terms: long-read sequencing, structur...

Wijngaard R et al., The American Journal of Human Genetics - Researchers describe seven individuals with monoallelic PSMB8 missense variants that impair immunoproteasome assembly, causing early-onset immunodeficiency and variable systemic inflammation via a dominant-negative mechanism. Key terms: PSMB8, immunoproteasome, PRAAS-ID, immunodeficiency, proteasome assembly. Study Highlights: Seven indi...

Malbranke C et al., Proceedings of the National Academy of Sciences (PNAS) - ProteomeLM is a transformer-based language model trained on complete proteomes that produces contextualized protein embeddings and attention signals which recover protein–protein interactions unsupervised and support supervised PPI and gene essentiality prediction across diverse taxa. Key terms: proteome language model, p...

Ortiz-Rodríguez M et al., Proceedings of the National Academy of Sciences (PNAS) - Single-molecule optical tweezers and fluorescence reveal how the S. pombe Pif1-family helicase Pfh1 alternates ATP-dependent unwinding and ATP-modulated rewinding at replication-fork-like substrates, and how mitochondrial SSB spRim1 tunes those activities. Key terms: Pfh1 helicase, Pif1-family, DNA unwinding, spRim1...

Douzgou Houge S et al., Human Genetics and Genomics Advances - This paper reports six individuals with biallelic loss-of-function DSCAM variants, delineating a recessive syndrome of moderate-to-severe neurodevelopmental delay with poor language, early focal seizures, hypotonia, short stature, and characteristic rotatory/vertical nystagmus with cone-pathway retinal dysfunction. Key terms: DSCAM, ne...

Wu X et al., Nature Biotechnology - The authors engineer synthetic PAM-containing DNA guides (crDNA) that bind Cas12a to form a deoxyribonucleoprotein (DNP) complex that recognizes and cleaves complementary RNA. Structural, biochemical and cellular data define a PAM-dependent activation route distinct from canonical RNA-guided systems and demonstrate applications in sensitive diagnostics and intra...

McGowan J et al., PLOS Genetics - Genome and transcriptome sequencing of an uncultured Oligohymenophorea ciliate (PL0344) reveals a novel nuclear genetic code in which UAA translates as lysine and UAG as glutamic acid, supported by suppressor tRNAs and phylogenomic context. Key terms: genetic code, ciliate, UAA, UAG, suppressor tRNA. Study Highlights: The authors assembled a macronuclear genome fr...

Kajonius PJ et al., Scientific Reports - This episode examines a twin-study analysis from the German TwinLife panel showing that cognitive ability at age 23 predicts socioeconomic status at age 27, and that much of this longitudinal association is explained by genetic factors rather than shared or unique environments. Key terms: cognitive ability, IQ, socioeconomic status, genetics, twin study. St...

Han et al., Nature Communications - This study uses paired single-nucleus chromatin accessibility and gene expression profiling across Alzheimer’s disease, Pick’s disease and progressive supranuclear palsy to map disease-dynamic cis-regulatory elements (CREs). Dynamic chromatin changes concentrate genetic risk in glial cell states and co-regulated regulatory modules. Integrating GWAS, sn-eQTLs and...

Yang X et al., Proceedings of the National Academy of Sciences - Genetic and pharmacologic inhibition of ICMT suppresses proliferation, invasion, and tumor growth in BRAFV600E-driven models and identifies INPP5E as an ICMT-dependent CAAX substrate whose membrane targeting supports melanoma growth. Key terms: ICMT, INPP5E, BRAFV600E, melanoma, UCM-1336. Study Highlights: ICMT genetic knockdown or p...

White MC et al., PNAS - This episode reviews a PNAS study showing that the kinase NEK2 is upregulated by EBV and its latency proteins and that NEK2 inhibition with the irreversible inhibitor JH295 selectively kills EBV-positive non-Hodgkin lymphoma cells, lowers drug resistance, and reduces tumor burden in mouse models. Key terms: NEK2, EBV, non-Hodgkin lymphoma, LMP1, drug resistance. Study Highl...

Jhaldiyal A et al., PNAS - This episode summarizes a PNAS study showing that PARP1 activation links Aβ1-42 toxicity to DNA damage, amyloid accumulation, neuroinflammation, and cognitive deficits, and that genetic or pharmacologic PARP1 suppression reduces pathology in cells and 5XFAD mice. Key terms: PARP1, poly(ADP-ribose), Alzheimer's disease, amyloid beta, neurodegeneration. Study Highlights: C...

Singh P et al., PNAS - This paper compares alternative splicing (AS) and gene expression (GE) across 200 transcriptomes from oral and pharyngeal jaws of 18 haplochromine cichlid species across Lakes Victoria, Malawi, and Tanganyika. The authors show that rapid changes in AS, often from low-frequency ancestral isoforms and some novel isoforms, contributed more to early trophic diversification than...

Han YJ et al., Proceedings of the National Academy of Sciences (PNAS) - This episode examines a PNAS study showing that the BRCA1 pseudogene BRCA1P1 produces circular RNAs that suppress antiviral innate immunity in human cancers; depleting BRCA1P1 activates interferon-stimulated genes, increases apoptosis and chemosensitivity, and enhances immune clearance in preclinical models. Key terms: BRCA1P1...

Bourgeois et al., Nature Communications - This study used enhanced CRISPR base editor screens, structural biology, biochemical assays, and in vitro/in vivo selection to map MEN1 mutations that drive resistance to five clinical menin inhibitors and to explain their mechanisms. Key terms: MEN1, menin inhibitors, CRISPR base editing, drug resistance, KMT2A. Study Highlights: CRISPR base editor screen...

Kalinowski A et al., PNAS - This study reports that C4 protein is enriched in human neutrophils and monocytes and that neutrophil C4 protein levels correlate with C4A gene copy number specifically in people with schizophrenia, linking peripheral innate immunity to disease-related biology. Key terms: schizophrenia, complement C4, neutrophils, monocytes, innate immunity. Study Highlights: Using publ...

Zhou Z et al., Nature Communications - This study develops a Lorentzian deconvolution model of cfDNA fragment length distributions across bodily fluids, identifies a ~159 bp component that demarcates intra- vs inter-nucleosomal fragments, and shows that intra-nucleosomal fragmentation entropy distinguishes tumor-derived ctDNA from non-tumor shortening. Key terms: cell-free DNA, fragmentomics, nucl...

Kearns FL et al., PNAS - Simulations and HDXMS reveal how the D614G substitution alters internal communication in SARS-CoV-2 spike, enabling faster receptor-binding-domain opening through newly engaged allosteric pathways. Key terms: D614G, SARS-CoV-2 spike, RBD opening, allostery, weighted ensemble simulations. Study Highlights: Weighted ensemble simulations of Ancestral, Delta, and Omicron BA.1...