Base by Base

Migeot J et al., Nature Communications - Large multicenter study linking a multidimensional social exposome (education, food insecurity, finances, healthcare access, childhood experiences) to cognition, function, neuropsychiatric symptoms, brain atrophy and connectivity in AD, FTLD and healthy aging across six Latin American countries. Key terms: social exposome, dementia, Latin America, brain con...

Hentze MW et al., Cell - A review that examines the expansion of the RNA-binding proteome, evaluates evidence for many non-canonical RBPs, and highlights riboregulation as an emerging mechanism by which RNA controls protein function, complexes, and metabolism. Key terms: RNA-binding proteins, non-canonical RBPs, riboregulation, intrinsically disordered regions, RNA interactome. Study Highlights: L...

Jassim A et al., Cancer Cell - This episode summarizes Jassim et al.'s introduction of RECODR, a graph-embedding pipeline that measures gene co-expression context drift from sc/snRNA-seq to reveal drivers of tumorigenesis and treatment resistance and to nominate combination therapies validated in mouse models and predicted for human tumors. Key terms: RECODR, gene context drift, single-cell RNA-se...

Rees J et al., The American Journal of Human Genetics - Rees et al. analyze signatures of positive selection in 276 genes linked to 13 dietary micronutrients across 40 global populations (HGDP). Using simulations and complementary selection scans, they report widespread local and oligogenic adaptation, with notable signals for zinc, iodine, and selenium. Key terms: micronutrients, positive selecti...

Wenzel M et al., Cell Genomics - This episode reviews a single-cell transcriptional atlas comparing Barrett's esophagus, intestinal metaplasia, normal esophagus/gastric samples and esophageal adenocarcinoma. The study uses single-cell RNA profiling and UMAP clustering to resolve epithelial, stromal and immune cell populations, identify gastric-like and intestinal metaplasia cell states, and charac...

Minich JJ et al., Cell - Minich et al. apply PacBio and Oxford Nanopore long‑read metagenomics to generate 986 complete metagenome‑assembled genomes from Malawian toddler fecal samples, then use pangenome analyses, mGWAS and machine learning to link microbial genes, strains and genome stability to child linear growth and breastfeeding. Key terms: long-read metagenomics, cMAGs, pangenome, pediatric...

Grist E et al., Cell - Large-scale transcriptome profiling of 1,523 diagnostic prostate tumors from randomized STAMPEDE phase 3 trials linked expression signatures and immunohistochemistry to 14-year survival. The Decipher RNA classifier was both prognostic and predicted survival benefit from docetaxel in metastatic disease, and a transcriptome-based PTEN inactivity classifier identified docetaxel...

Fogarty EC et al., Cell (187:1206–1222, February 29, 2024) - This episode summarizes Fogarty et al. 2024, which characterizes pBI143, a 2.7 kb cryptic plasmid that is highly prevalent and abundant across industrialized human gut metagenomes. The team combines large-scale metagenomics, isolate experiments, structural analyses, qPCR assays, and gnotobiotic mouse work to map pBI143’s distribution, tr...

Baya NA et al., The American Journal of Human Genetics - This episode summarizes a multi-modal study that integrates exome sequencing in 402,375 UK Biobank participants with CRISPR knockdown in human white adipocytes to nominate genes and pathways that alter overall adiposity and fat distribution. Key terms: obesity, fat distribution, exome sequencing, CRISPR knockdown, adipocytes. Study Highlight...

Dishuck PC et al., Cell Genomics - Using 169 long-read human haplotypes and 1.4 billion full-length cDNA reads, Dishuck et al. resolve the complex NPIP gene family on chromosome 16, revealing extreme copy-number and structural variation, widespread interlocus gene conversion and inversions, ongoing positive selection at specific paralogs, and paralog-specific full-length gene models with tissue-bi...

Adami A et al., Cell Genomics - This episode covers analyses of L1 retrotransposon subfamilies (L1PA2/3/4, L1HS), their chromatin signatures (including H3K4me3), and perturbation experiments using CRISPRi. The source text includes comparative plots across primates and gene-level readouts such as PPP1R1C. Key terms: L1 retrotransposon, L1PA2, L1HS, H3K4me3, CRISPRi. Study Highlights: The paper maps...

Díaz-Navarro A et al., Cell Genomics - OncoGAN is a multimodel generative AI pipeline that simulates realistic, privacy-preserving cancer genomes (VCFs, CNAs, SVs) across eight tumor types to support benchmarking and training of genome-analysis tools. Key terms: OncoGAN, synthetic genomes, generative AI, mutational signatures, privacy-preserving. Study Highlights: OncoGAN combines GANs, TVAEs, CTG...

Lee Y et al., The American Journal of Human Genetics - This episode reviews a study using hiPSC-derived 2D cortical neurons and 3D cortical organoids from individuals with del(17)p11.2 (Smith-Magenis syndrome) to map chromatin, transcriptional, developmental, and electrophysiological consequences of the deletion. Key terms: Smith-Magenis syndrome, del(17)p11.2, hiPSC organoids, chromatin topology,...

Blauwendraat C et al., The American Journal of Human Genetics - This episode reviews a perspective on the Global Parkinson’s Genetics Program (GP2), a coordinated international effort to expand Parkinson disease genetic discovery across underrepresented populations by combining large-scale genotyping, sequencing, capacity building, and open data sharing. Key terms: Parkinson's disease, genetics, g...

Ratajczak F et al., The American Journal of Human Genetics - This study uses the Speos graph machine-learning framework on multi-modal molecular networks to identify core genes for complex traits, focusing on ulcerative colitis (UC). It shows tissue-specific core-gene expression, coordinated regulation of core genes after perturbation, and frequent non-linear interactions in co-perturbations. Key...

Fielder SM et al et al., EMBO Molecular Medicine - This episode examines a study that identifies de novo heterozygous missense variants in ATP5F1A that cause developmental and movement disorders by destabilizing mitochondrial complex V. Functional C. elegans modeling and patient-cell assays reveal a dominant negative mechanism and uncoupled oxidative phosphorylation. Key terms: ATP5F1A, complex V,...

Urda-García B et al., PNAS - This episode discusses a PNAS study that builds disease similarity networks from public RNA-seq data and shows that stratifying patients into 'meta-patients' uncovers molecular mechanisms behind many medically observed comorbidities. Key terms: transcriptomics, comorbidity, disease networks, patient stratification, immune system. Study Highlights: The authors used unif...

Keahia DL et al., Proceedings of the National Academy of Sciences (PNAS) - This study shows that G-quadruplex (G4) DNA structures are hotspots of replication stress and mutagenesis in BRCA2-deficient cerebellar granule cell progenitors (GCPs), driving SHH-subgroup medulloblastoma, and identifies upregulation of the G4-resolving helicase PIF1 in tumors. Key terms: BRCA2, G-quadruplexes, PIF1, medul...

Cuddapah VA et al., Proceedings of the National Academy of Sciences (PNAS) - An international series of 10 individuals with ultrarare heterozygous BMAL1 variants present a syndromic neurodevelopmental phenotype (developmental delay, autism, variable sleep issues, seizures, marfanoid features). Functional assays in human cells and Drosophila show both loss- and gain-of-function effects on BMAL1 act...

Waisertreiger I et al., PNAS - This study tests how stabilization of G-quadruplex (G4) DNA by ligands such as pyridostatin (PDS) affects genome stability in primary and malignant B cells. The authors map PDS-induced chromosomal breaks and fusions to ribosomal DNA (rDNA) and pericentromeric major satellite (MaSat) repeats and link G4 stabilization to tetraploidization in cells lacking G2/M arrest....

️ Episode 118: Cancer cells subvert the primate-specific KRAB zinc finger protein ZNF93 to control APOBEC3B In this episode of PaperCast Base by Base, we explore how cancer cells co-opt a primate-specific KRAB zinc finger protein, ZNF93, to fine-tune the mutagenic enzyme APOBEC3B and manage replication stress. Study Highlights: Using genome-wide KZFP binding maps, CUT&Tag, RNA-seq, and functio...

Pol III–linked polyadenylation fuels SINE RNA accumulation during infection Music: Enjoy the music based on this article at the end of the episode. DOI: 10.1073/pnas.2507186122 Support: Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, stru...

Lareau CA et al., PNAS - Single-cell multiomic profiling identifies a mosaic synonymous mtDNA variant (m.7076A>G) in MT-CO1 that is selectively depleted in CD8+ effector memory T cells. Mechanistic assays show the variant forces wobble decoding, stalls mitochondrial ribosomes, and impairs differentiation of high-demand effector T cells. Key terms: mitochondria, synonymous mutation, mtDNA, CD8+...

Vasudevan HN et al., PNAS - CRISPRi, transcriptomic and proteomic profiling in peripheral nervous system cell models reveal how NF1 loss rewires Ras signaling, alters MEK inhibitor response, and nominates KRAS as a direct neurofibromin effector and therapeutic target. Key terms: neurofibromin, NF1 loss, KRAS, MEK inhibitor, SHP2 SOS2 compensation. Study Highlights: Repressing NF1 in immortalized p...

Barra MJ et al et al., Nature Communications (2025) 16:7295 - This study reports development and analytic evaluation of an extraction-free DARQ LAMP assay detecting HPV16, HPV18, and HPV45 plus a cellular control with a <1 hour sample-to-answer workflow on a low-cost benchtop heater/fluorimeter. Clinical testing in Houston (n=38) and Maputo (n=191) showed 100% and 93% concordance, respectively,...