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White R et al., F1000Research - Investigation of chimeric reads in MinION nanopore sequencing of short PCR amplicons, focusing on ligation-related artifacts, barcode tracing, and the prevalence of cross-gene chimeras in murine Ifna/Ifnb sequencing runs.

Music:
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Article title:
Investigation of chimeric reads using the MinION

First author:
White R

Journal:
F1000Research

DOI:
10.12688/f1000research.11547.2

Reference:
White R, Pellefigues C, Ronchese F, Lamiable O, Eccles D. Investigation of chimeric reads using the MinION [version 2; peer review: 2 approved]. F1000Research. 2017;6:631. https://doi.org/10.12688/f1000research.11547.2

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

QC:
This episode was reviewed as a special editorial release.

QC Scope:
- human-authored narration, music, and publication metadata
- excludes automated single-article AI QC because this episode was not produced by the standard AI narration pipeline
- source attribution and descriptive metadata were reviewed manually

QC Summary:
- production mode: human-written and human-produced episode
- automated transcript-vs-paper AI QC: not applicable
- metadata, source attribution, and release assets were reviewed manually

Metadata Audited:
- article_doi
- article_title
- article_journal
- reference
- license

Factual Items Audited:
- episode classified as a human-produced release
- canonical human narration retained as the source of record
- canonical human-produced music retained as the source of record
- automated NotebookLM regeneration intentionally not used for this episode

QC result: Editorial exception. This episode was approved after manual review.

Sun C et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2524504123 - Using cryo-EM and mass spectrometry in rat cerebellum, α1- and α6-containing GABAA receptor assemblies (β‑α‑β‑α‑γ stoichiometry) and PZ-II-029 binding were defined. Key terms: GABAA receptor, cerebellum, α6 subunit, cryo-EM, pyrazoloquinolinone.

Study Highlights:
The study used rat cerebellum tissue and combined confocal immunofluorescence, affinity purification with mass spectrometry, and high-resolution cryo-EM to characterize native α1-containing GABAA receptors. Cryo-EM classification resolved eight distinct α1-containing receptor assemblies that conform to a conserved β-α-β-α-γ arrangement and include previously unreported α6-containing heteromers. Structural models of α6-containing receptors show near-symmetric ECD architecture with conserved GABA-binding geometry and distinct electrostatic differences that may affect ligand kinetics. Binding of the α6-selective pyrazoloquinolinone PZ-II-029 at α+/γ− pockets was visualized and found to induce coordinated outward expansion of the extracellular domain, providing a structural basis for subtype-selective modulation.

Conclusion:
Native α1-containing cerebellar GABAA receptors adopt a conserved β-α-β-α-γ pentameric scaffold that includes α6 subunits and binds PZ-II-029 at α+/γ− sites, producing extracellular domain expansion.

Music:
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Article title:
Molecular assemblies and pharmacology of cerebellar GABAA receptors

First author:
Sun C

Journal:
Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2524504123

DOI:
10.1073/pnas.2524504123

Reference:
Sun C, Jahncke JN, Wright KM, Gouaux E. Molecular assemblies and pharmacology of cerebellar GABAA receptors. Proc. Natl. Acad. Sci. U.S.A. 2026;123:e2524504123. Published February 6, 2026. https://doi.org/10.1073/pnas.2524504123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/cerebellar-gabaa-alpha6-assemblies

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-12.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited sections cover GABAAR architecture, cerebellar α1/α6 coassembly, native purification and mass spectrometry, cryo-EM assembly identification, PZ-II-029 binding and allosteric effects, ligand-pocket differences, and study limitations.
- transcript topics: GABAAR architecture and subunit diversity; Cerebellar distribution of α1 and α6 subunits and mixed α1/α6 assemblies; Native cerebellar receptor purification, nanodisc reconstitution, and mass spectrometry findings; Cryo-EM identification of eight cerebellar GABAAR assemblies and β2-α1-β1-α6-γ2 configuration; PZ-II-029 binding at α+/γ− pockets (α1/γ2 and α6/γ2) and structural consequences; Ligand-induced extracellular-domain expansion and intersubunit distance changes

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Native cerebellar GABAARs include mixed α1 and α6 subunits forming β2-α1-β1-α6-γ2 assemblies
- Eight distinct cerebellar GABAAR assemblies were identified, all conforming to a β-α-β-α-γ scaffold
- PZ-II-029 binds at benzodiazepine pockets at α+/γ− interfaces, including α1/γ2 and α6/γ2 pockets, with site-specific interactions
- PZ-II-029 binding induces expansion of the extracellular domain and increases intersubunit distances across subunits
- Ki of PZ-II-029 is about 4.2 ± 0.4 nM in cerebellar receptor preparations
- Delta subunit is detected by mass spectrometry but is not resolved in cryo-EM reconstructions; delta-containing assemblies remain unresolved

QC result: Pass.

Granata J et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2527303123 - In mESCs and defined in vitro assays, EPOP and MTF2 stimulate PRC2 methyltransferase activity and promote de novo H3K27me3 deposition with GA- or GCN-rich DNA preference. Key terms: EPOP, MTF2, PRC2, H3K27me3, DNA-sequence specificity.

Study Highlights:
The study used mouse embryonic stem cells with an EED-rescue system and recombinant in vitro assays including HMT assays, EMSA, and ChIP-seq to probe EPOP and MTF2 function. Biochemical HMT assays on oligonucleosomes and dinucleosomes show both EPOP and MTF2 directly stimulate PRC2 catalytic activity, with MTF2 preferentially enhancing activity and binding on GCN-rich linkers and EPOP on GA-rich linkers. ChIP-seq during EED rescue demonstrated that EPOP is dispensable for initial PRC2 recruitment but its knockout reduces de novo H3K27me3 deposition by ~50% and cooperates with MTF2 and JARID2. Together these data indicate linker DNA sequence within nucleation sites guides subcomplex-specific PRC2 binding and catalytic output, influencing spatial establishment of H3K27me3 domains.

Conclusion:
EPOP and MTF2 define distinct PRC2 subcomplexes that stimulate PRC2 catalytic activity in a chromatin-dependent, DNA-sequence-specific manner to direct de novo H3K27me3 deposition.

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Article title:
EPOP and MTF2 activate PRC2 activity through DNA-sequence specificity

First author:
Granata J

Journal:
Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2527303123

DOI:
10.1073/pnas.2527303123

Reference:
Granata J., Liu S., Popoca L., Oksuz O., Reinberg D. EPOP and MTF2 activate PRC2 activity through DNA-sequence specificity. Proc. Natl. Acad. Sci. U.S.A. 2026;123:e2527303123. https://doi.org/10.1073/pnas.2527303123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/epop-mtf2-prc2-sequence

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-11.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited transcript segments describing PRC2 function, EPOP/MTF2 cofactors, in vitro histone methyltransferase (HMT) assays, the EED rescue system and de novo recruitment, dinucleosome substrates with GA- and GCN-rich linker DNA, EMSA binding data, and the rheostat model of cofactors shaping genome-wide H3K27me3 pattern
- transcript topics: PRC2 function and H3K27me3 deposition; EPOP and MTF2 as PRC2 cofactors; In vitro PRC2 histone methyltransferase assays; EED rescue system and de novo PRC2 recruitment; Dinucleosome substrates with GA- and GCN-rich linker DNA; EMSA nucleosome binding and affinity

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- EPOP and MTF2 stimulate PRC2 histone methyltransferase (HMT) activity in vitro
- EPOP is dispensable for de novo PRC2 recruitment; MTF2 is essential for de novo recruitment
- EPOP knockout reduces de novo H3K27me3 deposition in vivo by ~50%
- GA-rich linker DNA favors EPOP; GC-rich (GCN) linker DNA favors MTF2 in dinucleosome contexts
- GA- and GCN-dinucleotide results reflect substrate-context (chromatin) specificity, not naked DNA binding
- EPOP requires nucleosomal DNA context to exhibit GA preference; naked GA DNA shows no preference

QC result: Pass.

Larsen BB et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2529505123 - Deep mutational scanning of the Nipah virus fusion protein F using pseudoviruses maps ~8,500 single-residue effects, showing F is highly constrained and identifying antibody-escape mutations. Key terms: Nipah virus, fusion protein F, deep mutational scanning, pseudovirus, antibody neutralization.

Study Highlights:
Using nonreplicative lentiviral pseudoviruses and deep mutational scanning, the authors measured the effects of 8,449 single amino-acid mutations to the Nipah virus F ectodomain on cell entry in CHO cells expressing bat ephrin-B3. Measurements were fit with global epistasis models and mapped onto prefusion and postfusion structures, revealing the fusion peptide, lateral surface patches, and hexameric-interface residues are highly constrained. The library was screened against six monoclonal antibodies, quantifying mutation-mediated decreases in neutralization and showing distinct resilience among antibodies; specific Hendra F residues (Q70K, R336K) explained loss or reduction of neutralization by 4H3 and 1A9. The data nominate candidate proline substitutions and other sites for prefusion stabilization and inform vaccine and therapeutic antibody selection.

Conclusion:
Nipah virus F is highly functionally constrained relative to RBP with specific surface-exposed and core residues critical for cell entry, and antibody neutralization varies by epitope, informing prefusion-stabilized immunogen and therapeutic antibody design.

Music:
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Article title:
Functional and antigenic constraints on the Nipah virus fusion protein

First author:
Larsen BB

Journal:
Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2529505123

DOI:
10.1073/pnas.2529505123

Reference:
Larsen BB, Harari S, Gen R, Stewart C, Veesler D, Bloom JD. Functional and antigenic constraints on the Nipah virus fusion protein. Proc. Natl. Acad. Sci. U.S.A. 2026;123:e2529505123. https://doi.org/10.1073/pnas.2529505123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/nipah-f-deep-mutational-map

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-10.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the scientific content presented in the transcript, focusing on Nipah virus F deep mutational scanning, functional/antigenic constraints, structural interpretation, stabilizing mutations, antibody resilience, and translational implications.
- transcript topics: Nipah virus F structure and function; Deep mutational scanning methodology; Pseudovirus system with bat ephrin receptors; Mutational constraint landscape of Nipah F; Fusion peptide and hexamer interface regions; Prefusion stabilization via proline mutations

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Nipah F is highly constrained; mutations mostly impair function
- Deep mutational scanning tested 8,449 single amino acid mutations (~98.2% coverage)
- F is more functionally constrained than RBP (RBP more mutationally tolerant)
- Fusion peptide and lateral surface/hexamer interfaces are highly constrained
- Proline substitutions can stabilize prefusion F (candidate stabilizing mutations identified)
- Monoclonal antibodies show varying resilience to F mutations; 1F2 and 2D3 retain neutralization more broadly

QC result: Pass.

Berazategui MA et al., Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2531377123 - ESBX (Tb927.3.1660) links RNA Pol I localization at the ESB to activation of the active BES and repression of inactive BESs in Trypanosoma brucei, supporting monoallelic VSG expression. Key terms: Trypanosoma brucei, ESBX (Tb927.3.1660), expression site body, variant surface glycoprotein, RNA polymerase I.

Study Highlights:
Using ESB1-guided proximity-dependent biotinylation proteomics, endogenous tagging and high-resolution fluorescence microscopy, RNAi knockdown, RNA-seq, and inducible overexpression in bloodstream-form Trypanosoma brucei, the authors identify Tb927.3.1660 (ESBX) as an ESB-specific protein. ESBX localizes adjacent to Pol I (RPA2) and ESB1 within the ESB with measured center separations of ~68–175 nm and contains predicted SUMO-interacting and BRCT domains. ESBX depletion causes loss of the extranucleolar Pol I ESB focus, reduced processive transcription from the active BES with larger decreases distal to the promoter, and derepression of inactive BESs with low-processivity transcripts, whereas ESBX overexpression weakly activates inactive BESs with processive transcription without forming extra ESBs. Together the data indicate ESBX integrates activation of the active BES with repression of inactive BESs, a mechanism that supports monoallelic VSG expression.

Conclusion:
Tb927.3.1660/ESBX is an ESB component required to integrate activation of the active BES with repression of inactive BESs, thereby supporting monoallelic VSG expression in bloodstream-form Trypanosoma brucei.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
A factor integrating transcription and repression of surface antigen genes in African trypanosomes

First author:
Berazategui MA

Journal:
Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2531377123

DOI:
10.1073/pnas.2531377123

Reference:
Berazategui MA, Wheeler RJ, Tiengwe C, Lansink LIM, Rudenko G, Sunter JD, Goodwin I, Gull K, Faria JRC, et al. A factor integrating transcription and repression of surface antigen genes in African trypanosomes. Proc. Natl. Acad. Sci. U.S.A. 2026.123:e2531377123. https://doi.org/10.1073/pnas.2531377123

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/esbx-esb-vsg-regulation

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-09.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited sections cover ESBX identification, ESB localization, functional knockdown and overexpression phenotypes, BRCT domain/phase separation discussion, transcriptional state model, and broader implications; not audited are full experimental methods or supplementary data in detail.
- transcript topics: ESBX identification by proximity labeling and transcriptomics; ESBX localization to ESB near Pol I, ESB1, VEX2; ESBX depletion effects: growth arrest, ESB disassembly, active BES down, inactive BES derepression; ESBX overexpression effects: activation of inactive BESs, no extra ESBs; BRCT domains and phase separation notion for ESBX; Transcriptional state model: FE state, trickle state, enhanced trickle (ET)

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- ESBX is Tb927.3.1660 and functions as an ESB component
- ESBX links transcriptional activation of the active BES with repression of inactive BESs
- ESBX depletion leads to ESB disassembly and loss of RNA Pol I at the ESB
- Inactive BES transcripts are derepressed upon ESBX depletion
- ESBX overexpression activates inactive BESs with processive transcription without forming extra ESBs
- ESBX is likely upstream of ESB1 and influences VEX2/ VEX-mediated exclusion

QC result: Pass.

Solomon CU et al., Nat Commun(2026). - Integrative analysis in human VSMCs identifies pleiotropic genes including FES that regulate vascular remodeling; pooled CRISPR and mouse knockout show FES loss increases MMPs, atherosclerosis and blood pressure. Key terms: FES, vascular smooth muscle cell, atherosclerosis, colocalization eQTL, CRISPR knockout screen.

Study Highlights:
The study used a large human umbilical cord‑derived VSMC eQTL bank (n=1,486) combined with colocalization (eCAVIAR, SMR/HEIDI), ATAC‑seq, DNA methylation, H3K27ac HiChIP and pooled CRISPR‑Cas9 knockout screens to nominate likely causal genes for CAD, hypertension, stroke and AAA. Pooled CRISPR screens and siRNA validation in VSMCs highlighted BCAR1, CARF, SMARCA4 and FES as modulators of VSMC proliferation or migration, while FES knockdown increased MMP1/MMP3, reduced contractile markers and promoted migration by RNA‑seq and proteomics/phosphoproteomics. In vivo, Fes‑/-/Apoe‑/- mice had larger en face aortic lesion areas (8.34±2.54% vs 6.06±2.35%, P=0.013) and higher baseline systolic/diastolic blood pressure (104.4±6.7 vs 88.0±10.1 mmHg and 74.9±9.0 vs 58.8±8.9 mmHg, P=0.042). These results support FES as a pleiotropic, potentially druggable regulator of VSMC phenotype with functional effects on atherosclerosis and blood pressure.

Conclusion:
Integrative functional genomics implicates panels of likely causal and pleiotropic genes, including FES, that regulate VSMC behavior and whose loss promotes VSMC dedifferentiation, increased MMP production, larger atherosclerotic lesions and higher blood pressure.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Integrative functional genomics analysis identifies pleiotropic genes for vascular diseases

First author:
Solomon CU

Journal:
Nat Commun(2026).

DOI:
10.1038/s41467-026-69273-8

Reference:
Solomon CU, McVey DG, Andreadi C, Peng G, Turner L, Song DSS, Zhang H, Lee DP, Karamanavi E, Yang W, Chu J, Chen R, Haworth KE, Anene-Nzelu CG, Li H, Denniff MJ, Li PY, Zhang Y, Huang X, Morris GE, Greer PA, Stringer EJ, Yu H, Foo RSY, Douglas G, Samani NJ, Webb TR, Ye S. Integrative functional genomics analysis identifies pleiotropic genes for vascular diseases. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69273-8

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/fes-vsmc-pleiotropic-genes

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-08.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited substantive portions of the transcript describing FES as a pleiotropic regulator of vascular disease, VSMC phenotypic switching, CRISPR knockouts, mouse model results, UK Biobank human genetics, and therapeutic implications.
- transcript topics: Pleiotropy across vascular diseases; FES as a master regulator in vascular smooth muscle cells (VSMCs); VSMC phenotypic switching, migration, and MMP production; Pooled CRISPR-Cas9 knockout screens and validation; Mouse model: Fes knockout and atherosclerosis/blood pressure; UK Biobank human genetics for FES variants

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 5
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- FES is identified as a pleiotropic gene affecting more than one vascular disease (CAD and hypertension).
- FES knockdown in vascular smooth muscle cells increases migration and production of matrix metalloproteinases (MMPs) and decreases contractile markers.
- Fes knockout mice on a high-fat diet show larger atherosclerotic lesions and elevated baseline blood pressure, with impaired vasodilation responses.
- UK Biobank data show deleterious FES variants associate with higher blood pressure and increased risks of hypertension and myocardial infarction.
- A set of pleiotropic genes (including FES) was identified; several are druggable and might be targeted to affect multiple vascular diseases.

QC result: Pass.

Ramírez Renta GM et al., The American Journal of Human Genetics, 113 (2026) 16-28. doi:10.1016/j.ajhg.2025.11.014 - GALS survey of >4,000 US respondents (GenPop and SPARK) shows confidence in genetic knowledge predicts Familiarity, Knowledge, and Skills, explaining ~25% of variance. Key terms: genetic literacy, confidence in knowledge, GALS, SPARK, science communication.

Study Highlights:
Using the Genetic and Autism Literacy Survey (GALS) in two US samples (GenPop and SPARK; n>4,000), the authors measured three genetic literacy components: Familiarity, Knowledge, and Skills via subjective familiarity ratings, objective true/false items, and a comprehension task. They modeled associations between these subscales and identity/belief measures including perceived importance, confidence, religiosity, religious affiliation, and political belief using linear regression adjusted for education and population. Confidence in one’s genetic knowledge was the strongest predictor, accounting for roughly 25% of variance in Familiarity and Knowledge and substantially improving model R2; perceived importance had a positive but smaller effect while religious and political measures showed mixed associations. The finding implies improving individuals’ confidence in genetic knowledge, alongside tailored communication strategies, could support better comprehension and uptake of genetics and genomics services.

Conclusion:
Confidence in one’s genetic knowledge, after education, is the largest modifiable predictor of genetic literacy and should be a focus for interventions to improve comprehension and uptake of genetics services.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Interaction of identity and beliefs with genetic literacy

First author:
Ramírez Renta GM

Journal:
The American Journal of Human Genetics, 113 (2026) 16-28. doi:10.1016/j.ajhg.2025.11.014

DOI:
10.1016/j.ajhg.2025.11.014

Reference:
Ramírez Renta GM, Little ID, Koehly LM, et al. Interaction of identity and beliefs with genetic literacy. The American Journal of Human Genetics. 2026;113:16–28. https://doi.org/10.1016/j.ajhg.2025.11.014

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/genetic-literacy-confidence-gals

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-07.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript’s presentation of core scientific claims: the three GL pillars (Familiarity, Knowledge, Skills), cultural cognition framework, GALS sampling (GenPop and SPARK), key findings on confidence as predictor, religion/politics effects, disengagement, and implications for communication and trust.
- transcript topics: Genetic literacy pillars (Familiarity, Knowledge, Skills); Cultural cognition theory and identity filtering; GALS methodology and cohorts (GenPop vs SPARK); Confidence as a key predictor (~25% variance in GL scores); Religion/religiosity and science vs religion conflict effects; Political beliefs and GL differences

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Genetic literacy comprises three components: Familiarity, Knowledge, and Skills.
- Confidence in one’s genetic knowledge is the strongest predictor of GL scores, accounting for about 25% of the variance.
- Religious affiliation and religiosity are negative predictors of GL scores (relative to non-religious groups).
- When faced with science-religion conflict, participants who chose science had higher GL scores than those who chose religion.
- Liberals show higher GL scores across subscales than conservatives or moderates; conservatives differ mainly on Knowledge.
- SPARK participants scored higher on GL measures than GenPop participants.

QC result: Pass.

Ramírez Renta GM et al., The American Journal of Human Genetics - GALS survey of >4,000 US respondents (GenPop and SPARK) shows confidence in genetic knowledge predicts Familiarity, Knowledge, and Skills, explaining ~25% of variance.

Study Highlights:
Using the Genetic and Autism Literacy Survey (GALS) in two US samples (GenPop and SPARK; n>4,000), the authors measured three genetic literacy components: Familiarity, Knowledge, and Skills via subjective familiarity ratings, objective true/false items, and a comprehension task. They modeled associations between these subscales and identity/belief measures including perceived importance, confidence, religiosity, religious affiliation, and political belief using linear regression adjusted for education and population. Confidence in one’s genetic knowledge was the strongest predictor, accounting for roughly 25% of variance in Familiarity and Knowledge and substantially improving model R2; perceived importance had a positive but smaller effect while religious and political measures showed mixed associations. The finding implies improving individuals’ confidence in genetic knowledge, alongside tailored communication strategies, could support better comprehension and uptake of genetics and genomics services.

Conclusion:
Confidence in one’s genetic knowledge, after education, is the largest modifiable predictor of genetic literacy and should be a focus for interventions to improve comprehension and uptake of genetics services.

Music:
Enjoy the music based on this article at the end of the episode.

Reference:
Ramírez Renta GM, Little ID, Koehly LM, et al. Interaction of identity and beliefs with genetic literacy. The American Journal of Human Genetics. 2026;113:16–28. https://doi.org/10.1016/j.ajhg.2025.11.014

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.castos.com/episodes/genetic-literacy-confidence-gals

Liang Y et al., The American Journal of Human Genetics, 113 (2026) 276-290. doi:10.1016/j.ajhg.2025.12.014 - TWAS using genetically predicted expression exhibit polygenicity-driven inflation that increases with GWAS sample size and heritability; a gene-specific variance-control correction yields calibrated p values. Key terms: transcriptome-wide association study, TWAS, polygenicity, variance-control, PrediXcan.

Study Highlights:
The authors evaluated TWAS and related xWAS using simulated polygenic null traits and UK Biobank genotypes with predicted mediators including gene expression, metabolites, and brain features. They combined large-scale simulations, theoretical derivations, and empirical regression of mean Z2 on N*h2δ to estimate a gene-specific inflation slope Φ and applied corrections with S‑PrediXcan/PrediXcan across 110 GWAS traits. They show analytically and empirically that Var(Z) ≈ 1 + N*h2δ*Φ, observe a cohort-level slope around 4.2×10^-5, and demonstrate that dividing Z by sqrt(1+N*h2δ*Φ) restores calibration. Applying the variance-control correction yields well-calibrated p values, reduces false positives for highly polygenic traits, and improves precision with minimal loss of power.

Conclusion:
A gene-specific variance-control correction based on an empirically estimated inflation slope Φ corrects polygenicity-driven inflation in TWAS/xWAS and yields calibrated false-positive rates in simulations and real GWAS analyses.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
A gene-specific variance-control approach corrects polygenicity-driven inflation observed in transcriptome-wide association studies

First author:
Liang Y

Journal:
The American Journal of Human Genetics, 113 (2026) 276-290. doi:10.1016/j.ajhg.2025.12.014

DOI:
10.1016/j.ajhg.2025.12.014

Reference:
Liang Y, Nyasimi F, Im HK. A gene-specific variance-control approach corrects polygenicity-driven inflation observed in transcriptome-wide association studies. The American Journal of Human Genetics. 113 (2026) 276-290. https://doi.org/10.1016/j.ajhg.2025.12.014

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/twas-variance-control-inflation

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-06.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Substantive audit of the transcript’s treatment of TWAS inflation, the Phi inflation parameter, the variance-control correction, and real-data validation across multiple data modalities.
- transcript topics: TWAS/xWAS inflation due to polygenicity; linear scaling of inflation with sample size and trait heritability; gene-specific inflation parameter Phi (Φ); variance-control correction and Z-score calibration (Zcorr = Ztwas / sqrt(1 + Φ N h2δ)); comparison with BACON correction; simulation framework: polygenic null trait; UK Biobank data usage across metabolites and brain features

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- TWAS/xWAS inflation increases with polygenicity
- Inflation scales linearly with GWAS sample size and trait heritability
- Gene-specific inflation parameter Phi (Φ) modulates inflation per gene
- Variance-control method calibrates Z-scores by adjusting with sqrt(1 + Φ N h2δ)
- Variance-control yields calibrated p-values and reduces false positives in polygenic contexts
- Real-data validation across 110 GWAS traits and across metabolites/brain features

QC result: Pass.

Di Donato N et al., The American Journal of Human Genetics, 113 (2026) 324-341. doi:10.1016/j.ajhg.2025.12.007 - Analysis of 290 individuals with ACTB and ACTG1 variants defines eight distinct non-muscle actinopathies and links BWCFF-causing variants to altered actin polymerization dynamics. Key terms: ACTB, ACTG1, Baraitser-Winter, actin polymerization, genotype-phenotype.

Study Highlights:
The study assembled a clinical-genomic cohort of 290 individuals with P/LP ACTB or ACTG1 variants and used expert phenotyping plus GestaltMatcher facial analysis to delineate eight distinct non-muscle actinopathies. Complementary methods included patient-derived fibroblast transcriptomics, recombinant actin production, differential scanning fluorimetry, and pyrene-based polymerization/depolymerization assays. BWCFF-associated missense variants (e.g., ACTB:R196H, ACTG1:T203M) produced decreased polymerization rates and faster depolymerization, whereas selected ACTB missense or in-frame variants impaired folding or thermal stability consistent with loss-of-function. These mechanistic stratifications support improved diagnostic classification, prognostication, and selection of functional assays for variant interpretation.

Conclusion:
Variant-level analysis of 290 individuals delineates eight distinct non-muscle actinopathies and shows that BWCFF-linked missense variants disrupt actin polymerization while select ACTB variants cause protein instability consistent with loss-of-function.

Music:
Enjoy the music based on this article at the end of the episode.

Article title:
Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies

First author:
Di Donato N

Journal:
The American Journal of Human Genetics, 113 (2026) 324-341. doi:10.1016/j.ajhg.2025.12.007

DOI:
10.1016/j.ajhg.2025.12.007

Reference:
Di Donato N, NMA Consortium, et al. Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies. The American Journal of Human Genetics. 113:324-341 (2026). https://doi.org/10.1016/j.ajhg.2025.12.007

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) - https://creativecommons.org/licenses/by/4.0/

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, structural genomics, and proteomics.

Episode link: https://basebybase.com/episodes/actb-actg1-non-muscle-actinopathies

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-02-06.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the substantive scientific content of the transcript, focusing on: gene pair ACTB/ACTG1; eight NMAs; BWCFF mechanistic basis (actin polymerization/depolymerization); loss-of-function ACTB with thrombocytopenia; ACTG1 deletion phenotypes; fibroblast/tissue specificity; GestaltMatcher-based facial analysis; diagn
- transcript topics: ACTB and ACTG1 gene similarity and functional differences; Cohort overview: 290 individuals, 125 new cases; Eight non-muscle actinopathies (NMAs) and genotype-phenotype correlations; BWCFF mechanism: missense variants cause unstable actin, altered polymerization/depolymerization; ACTB loss-of-function (LoF) disorder: thrombocytopenia and neurodevelopmental features; ACTG1 deletions: milder phenotypes or near-normal presentations

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 7
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- Cohort comprises 290 individuals with ACTB/ACTG1 variants (125 new cases)
- Eight distinct non-muscle actinopathies (NMAs) identified
- BWCFF associated with missense variants showing decreased actin polymerization and faster depolymerization
- ACTB loss-of-function (LoF) variants/deletions associated with thrombocytopenia and mild neurodevelopmental impairment
- ACTG1 deletions often milder or near-normal; dosage sensitivity lower than ACTB
- Dystonia-deafness syndrome (ACTB hotspot variants like R183W) and isolated hearing loss (ACTG1) described

QC result: Pass.