Base by Base

Gustavo Barra
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Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

  1. vor 3 Std.

    416: HGT-chimeras: fusion across the tree of life

    Kapoor RR et al., PNAS - A systematic screen of 319 arthropod genomes reveals genes formed by in‑frame fusion of horizontally transferred nonmetazoan sequences with endogenous metazoan regions. Many of these HGT-chimeras are transcribed, conserved, and show coherent domain architectures, implicating them in diverse biological processes. Key terms: horizontal gene transfer, gene fusion, arthropods, novel genes, molecular evolution. Study Highlights: The authors developed an intragenic phylogenetic pipeline and screened 319 high-quality arthropod genomes to identify HGT-chimeras. They report 274 chimeric genes corresponding to 104 independent origination events derived from bacteria, viruses, fungi, and plants. RT-PCR and Sanger sequencing validated contiguous chimeric mRNA expression for 36 of 41 tested chimeras, and molecular evolution analyses show widespread purifying selection and functional domain assembly. Evidence indicates gene duplication and postfusion divergence often accompany chimera formation, suggesting a recurrent route to novel gene functions. Conclusion: Fusion of horizontally acquired sequences with endogenous metazoan sequences has been a recurrent source of novel genes in arthropods, producing expressed, conserved chimeric proteins that likely contribute to organismal biology and evolution. Music: Enjoy the music based on this article at the end of the episode. Article title: Evolutionary innovation through fusion of sequences from across the tree of life First author: Kapoor RR Journal: PNAS DOI: 10.1073/pnas.2602557123 Reference: Kapoor RR, Rona I, Extavour CG, et al. Evolutionary innovation through fusion of sequences from across the tree of life. Proc Natl Acad Sci U S A. 2026;123(29):e2602557123. doi:10.1073/pnas.2602557123 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/hgt-chimeras-fusion-across-tree-of-life QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-18. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript's core scientific narrative: definition and existence of HGT-chimeras in arthropods; the 319-genome screen; 274 chimeras in 104 origination events; RT-PCR validation (36/41 across 18 species); evidence of purifying selection (dN/dS 1) and selected exemplars (shrimp, copepod, damselfly, mosquito - transcript topics: HGT-chimera concept and definition; Scope of arthropod genome survey (319 genomes); Quantitative results (274 chimeras, 104 origination events, 109 HGT intervals); RT-PCR validation and transcriptional evidence (36/41 across 18 species); Purifying selection and dN/dS interpretation; Exemplar cases: shrimp cluster 12, copepod cluster 14, damselfly cluster 41, mosquito cluster 9 QC Summary: - factual score: 10/10 - metadata score: 10/10 - supported core claims: 4 - claims flagged for review: 0 - metadata checks passed: 4 - metadata issues found: 0 Metadata Audited: - article_doi - article_tit...

  2. vor 5 Std.

    415: ERG Unlocked: Targeting the PNT Domain with PBITE-1

    PNAS - This episode breaks down a PNAS study that identifies a druggable pocket in the ERG transcription factor PNT domain and describes PBITE-1, a small-molecule probe that binds this pocket to inhibit ERG-driven prostate cancer models. Key terms: ERG, PNT domain, PBITE-1, prostate cancer, small-molecule inhibitor. Study Highlights: The authors show that TMPRSS2:ERG-positive prostate cancer cells remain dependent on ERG for survival and tumor maintenance. A domain-focused DSF screen identified F0341 as a PNT-domain binder and SAR optimization yielded PBITE-1, which engages a solvent-exposed pocket spanning two helices and a flexible loop. PBITE-1 selectively stabilizes ERG in cells, suppresses ERG target genes, reduces proliferation and invasion, induces apoptosis in ERG-positive cell lines and organoids, and triggers tumor cell apoptosis in VCaP xenografts. Conclusion: The ERG N-terminal PNT domain contains a structurally coherent, ligandable pocket; PBITE-1 provides proof-of-concept that ERG can be directly targeted by small molecules, laying groundwork for future ERG-directed inhibitors and degrader strategies for TMPRSS2:ERG-driven cancers. Music: Enjoy the music based on this article at the end of the episode. Article title: A ligandable PNT domain establishes ERG as a directly targetable oncogenic driver in prostate cancer Journal: PNAS DOI: 10.1073/pnas.2537437123 Reference: https://doi.org/10.1073/pnas.2537437123 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/erg-pnt-pbite-1 QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-18. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript sections describing ERG dependency in TMPRSS2:ERG-positive prostate cancer, DSF screening and hit identification (F0341), SAR optimization to PBITE-1, binding and target engagement assays (NMR, BLI, CETSA), cellular effects (viability, apoptosis, ERG target gene suppression), organoid and in vivo - transcript topics: ERG dependency in TMPRSS2:ERG-positive prostate cancer; Domain-focused differential scanning fluorimetry (DSF) screen; PBITE-1 discovery and SAR optimization; PBITE-1 binding interface mapping to ERG PNT domain (NMR, docking, H2/H6); Target engagement and cellular effects (CETSA, cell viability, apoptosis, ERG target genes); Organoid and in vivo VCaP xenograft data 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: - TMPRSS2:ERG fusion occurs in approximately 50% of prostate cancers in patients of European ancestry. - PBITE-1 engages a discrete solvent-exposed surface within the ERG PNT domain, defining a ligand-binding pocket. - PBITE-1 directly binds the ERG PNT domain and stabilizes full-length ERG in cell...

  3. vor 1 Tag

    414: Durability of Cas9 Gene Drives in Anopheles: A 2‑Year Cage Study

    Carballar-Lejarazúa R et al., PNAS (2026) - This episode summarizes a 2-year, 35-generation multireplicate cage trial evaluating three autonomous Cas9/gRNA gene-drive strains (AcTP13, AcTP43 in Anopheles coluzzii; AgTP13 in Anopheles gambiae). The study tracked drive inheritance, cassette integrity, resistance allele emergence, off-target activity, and sustained antiparasite efficacy against Plasmodium falciparum. Key terms: gene drive, Anopheles, Cas9/gRNA, parasite suppression, long-term stability. Study Highlights: Over 2 years (35 generations) triplicate cage trials of three Cas9/gRNA gene-drive strains monitored drive dynamics, cassette integrity, resistance, off-target effects, and parasite suppression. All A. coluzzii replicates achieved rapid fixation and remained stable; two AgTP13 replicates fixed while one accumulated a functional cleavage-resistant allele that reduced drive frequency. Effector transgene sequences and mRNA expression were largely preserved, though one AcTP43 replicate lost a TP10 monomer copy. Parasite challenge assays at low and medium-low gametocytemias showed significant reductions in oocyst and sporozoite prevalence and intensity. Conclusion: Multimetric longitudinal data show that Cas9/gRNA-based population-modifying drives can remain genetically stable and retain antiparasite activity over a 2-year period in laboratory Anopheles populations, with replicate-level resistance emergence underscoring the need for replicated risk assessment and monitoring. Music: Enjoy the music based on this article at the end of the episode. Article title: Long-term stability and performance of Cas9/guide RNA-based gene drives in anopheline mosquitoes First author: Carballar-Lejarazúa R Journal: PNAS (2026) DOI: 10.1073/pnas.2605739123 Reference: Carballar-Lejarazúa R, Winokura L, Pham TB, Tushar T, Tao M, Dimopoulos G, James AA, et al. Long-term stability and performance of Cas9/guide RNA-based gene drives in anopheline mosquitoes. PNAS. 2026;123(28):e2605739123. doi:10.1073/pnas.2605739123 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/414-gene-drive-stability-anopheles QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-17. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript sections describing gene-drive mechanism, target-product profile criteria, long-term cage trials, molecular/cassette integrity, resistance emergence, off-target analysis, and parasite-suppression outcomes, with attention to quantitative results and limitations. - transcript topics: Gene-drive mechanism and inheritance (Cas9/gRNA, HDR); Target Product Profile (TPP) criteria for gene-drive systems; Long-term cage trial design (AcTP13, AcTP43 in Anopheles coluzzii; AgTP13 in Anopheles gambiae); Cargo design and tracking markers (CFP, mCherry) and antiparasite effectors (M1C3, M2A10, MultiEff, TP10, EPIP); Resistance emergence at the target site (AgTP13) and 3 bp insertion; Payload stability and tandem repeats (...

  4. vor 6 Tagen

    413: Rpc34 WH2 dynamics in RNA polymerase III

    Wu J-S et al., PNAS - A PNAS study using smFRET and nano-positioning triangulation maps dynamic positioning of the Rpc34 WH2 domain in yeast Pol III elongation complexes and presents a thiol-capping SPAAC labeling strategy to enable selective site-specific fluorophore attachment. Key terms: RNA polymerase III, Rpc34, winged helix, smFRET, bio-orthogonal labeling. Study Highlights: Using smFRET with ALEX and nano-positioning triangulation, the authors show Rpc34 WH2 occupies three discrete positions across the Pol III DNA-binding cleft and dynamically interconverts among them. A bio-orthogonal labeling workflow—azido-UAA incorporation plus SPAAC with thiol-capping—enabled selective labeling in the cysteine-rich complex. Maf1 binding locks WH2 into the upstream/distal state, validating positional assignments, and HMM dwell-time analysis revealed ordered transitions that proceed through the middle state with characteristic lifetimes. These results indicate Rpc34 WH2 engages the elongation complex via transient, weak DNA and protein contacts, with potential roles in bubble stabilization and rapid reinitiation. Conclusion: Rpc34 WH2 is a mobile, multifunctional cleft-associated module that occupies three ordered positions to transiently engage the Pol III elongation complex, and the thiol-capping SPAAC labeling approach provides a robust route for smFRET studies of large native assemblies. Music: Enjoy the music based on this article at the end of the episode. Article title: Dynamic positioning of Rpc34 winged helix in RNA polymerase III elongation complex for its stability with implications for reinitiation First author: Wu J-S Journal: PNAS DOI: 10.1073/pnas.2601775123 Reference: Wu J-S, Chang W-H, et al. Dynamic positioning of Rpc34 winged helix in RNA polymerase III elongation complex for its stability with implications for reinitiation. Proc Natl Acad Sci U S A. 2026;123(27):e2601775123. doi:10.1073/pnas.2601775123 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/base-by-base-413-rpc34-wh2-pol3-dynamics QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-12. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript portions describing Rpc34 WH2 dynamics, labeling strategy, three-state model, Maf1 effects, NPS localization, and rapid reinitiation implications, comparing to the original article. - transcript topics: Rpc34 WH2 dynamics in Pol III elongation complex; smFRET labeling strategy (azido-UAA, SPAAC, MMTS); Maf1 regulation of WH2 mobility; Nano-positioning system (NPS) localization; Three-state model: distal, middle, proximal; Implications for rapid reinitiation and Pol III processivity QC Summary: - factual score: 9/10 - 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 ...

  5. vor 6 Tagen

    412: Fault Lines in Forensic Proficiency Testing

    Scurich N et al., PNAS - A concise breakdown of a PNAS perspective that analyzes forensic proficiency testing practices using the 2023 CTS firearms test as a case study. The authors identify test design and administration flaws—easy items, consensus scoring, handling of inconclusives, nonblind verification, shot‑to‑shot variability, and contextual bias—that undermine claims about examiner accuracy and the utility of reported error rates for courts and laboratories. Key terms: forensic proficiency testing, firearm identification, false positive rate, test design, cognitive bias. Study Highlights: The authors analyze CTS Test 23‑5262 and report a false‑positive rate of about 20% for bullet comparisons, highlighting broader concerns. They identify structural issues in proficiency testing including ceiling effects from easy items, inconsistent scoring of inconclusives, reliance on consensus rather than ground truth, and nonblind verification. The paper argues these features confound examiner performance with test properties, limiting the tests’ ability to estimate operational error rates and inform court decisions. The authors recommend better test design, blind verification, confidence ratings, and use of objective metrics to improve validation and lab practice. Conclusion: Current forensic proficiency testing practices can conceal fundamental weaknesses in examiner performance and test design; systemic, evidence‑based reform is needed to provide courts and laboratories with meaningful estimates of reliability and to reduce risks of wrongful outcomes. Music: Enjoy the music based on this article at the end of the episode. Article title: Assessing the foundations of forensic identification evidence: A critical examination of proficiency test design and results First author: Scurich N Journal: PNAS DOI: 10.1073/pnas.2528192123 Reference: Scurich N, Albright TD. Assessing the foundations of forensic identification evidence: A critical examination of proficiency test design and results. PNAS. 2026; Vol.123:e2528192123. doi:10.1073/pnas.2528192123 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/fault-lines-forensic-proficiency-testing QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-12. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript sections describing CTS proficiency testing (Test 23-5262), the reported false-positive rates, consensus scoring and inconclusives, out-of-class eliminations, shot-to-shot variability and reproducibility, contextual bias and NIBIN leads, nonblind verification, signal detection theory as reform, a - transcript topics: CTS proficiency testing overview and purpose; CTS Test 23-5262 design and ground truth; False-positive rate findings (around 20%; 19.2% excluding item 4; 22% at least one false positive); Consensus scoring and handling of inconclusives; Out-of-class eliminations (Item 4) and associated errors; Class characteristics and reproducibility concerns across tes...

  6. 9. Juli

    411: EKV cells and the Human Prion Assay: a scalable platform for sCJD infectivity

    Nihata A et al., PNAS - This PNAS study describes the development of EKV, a humanized dividing cell line that propagates bona fide sporadic CJD (sCJD) prions, and the Human Prion Assay (HPA), a cell-based method that quantifies infectivity with sensitivity comparable to transgenic mouse bioassay while enabling rapid therapeutic screening. Key terms: sCJD, EKV cells, Human Prion Assay, prion infectivity, anti-PrP antibody. Study Highlights: The authors engineered EKV cells by reconstituting CAD5 PrP-knockdown cells with human PrP (V129) and iterative single-cell cloning to enrich prion susceptibility. EKV cells propagate de novo infectious sCJD prions that reproduce strain-specific pathology when transmitted to humanized Tg152c mice. The Human Prion Assay (HPA) using EKV cells quantifies sCJD infectivity across a wide dynamic range with sensitivity comparable to mouse bioassay but in weeks rather than years. Persistently infected iEKV clones can be cured by the anti-PrP monoclonal antibody ICSM18, validating the platform for high-throughput therapeutic screens. Conclusion: EKV cells and the HPA provide a renewable, scalable, and faster alternative to animal bioassays for measuring authentic human sCJD infectivity and for screening and validating anti-prion therapeutics, while retaining strain-specific biological properties. Music: Enjoy the music based on this article at the end of the episode. Article title: A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt–Jakob disease prions First author: Nihata A Journal: PNAS DOI: 10.1073/pnas.2600341123 Reference: Nihata A, Collinge J, Linehan J, Brandner S, Mead S, Schmidt C, Rayner MLD, Jat PS, Arora P, et al. A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt–Jakob disease prions. PNAS. 2026;123(27):e2600341123. doi:10.1073/pnas.2600341123. 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/ekv-human-prion-assay QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-09. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Substantive audit focused on EKV cell development and validation, in vitro propagation of human sCJD prions, HPA implementation and benchmarking against mouse bioassay, drug-screening demonstration, and documented limitations (codon 129 mismatch, occult infectivity). - transcript topics: Prion biology and strain concepts (PRNP codon 129 polymorphism); Historical barriers to human prion culture and need for cell-based infectivity assays; Engineering EKV cells: CAD5-KDB3, human PrP V129, mouse signal peptide; Iterative single-cell cloning and enrichment to EKV; Infectivity validation via transmission to Tg152c mice; Development and validation of the Human Prion Assay (HPA) QC Summary: - factual score: 10/10 - metadata score: 10/10 - supported core claims: 6 - claims flagged for review: 0 - metadata checks passed: 4 -...

  7. 8. Juli

    410: Nucleotide diversity is a poor predictor of short-term adaptive potential

    Abson KL et al., PNAS - A cross-species synthesis and theory paper showing that simple molecular diversity metrics poorly predict short-term adaptive potential. The authors compiled >2,100 quantitative genetics estimates (evolvability and heritability) across ~193 eukaryotic species and compared them to nucleotide diversity (π) and microsatellite heterozygosity (He). They find nucleotide diversity explains only ~1.1% of interspecific variation in evolvability and that doubling π corresponds to a modest ~11.7% increase in evolvability. Theoretical models indicate this weak relationship is expected when trait variance is shaped by stabilizing selection, mutation rates, and effective population size dynamics. Key terms: nucleotide diversity, evolvability, adaptive potential, conservation genetics, microsatellites. Study Highlights: The authors compiled 2,113 evolvability estimates across 193 eukaryotic species and matched these to measures of nucleotide diversity (π) and microsatellite heterozygosity (He). They found no meaningful association between ln(IA) (evolvability) and ln(π): π explained ~1.1% of interspecific variation and doubling π predicts only an ~11.7% increase in evolvability. Microsatellite and nucleotide diversity were uncorrelated across species, and both molecular measures were weak predictors of quantitative genetic variation. Theoretical mutation–selection–drift models show weak associations are expected under stabilizing selection and when VA depends more on mutation rate and selection than on neutral diversity. Conclusion: Simple, genome-wide molecular diversity metrics (π, He) are poor predictors of short-term adaptive potential (evolvability); conservation assessments should not rely on these alone and should incorporate trait-based or functionally informed genomic data. Music: Enjoy the music based on this article at the end of the episode. Article title: Nucleotide diversity is a poor predictor of short-term adaptive potential First author: Abson KL Journal: PNAS DOI: 10.1073/pnas.2536181123 Reference: Abson KL, Zijmers L, Mittell EA, Young EA, Postma E, Eyre-Walker A, Hadfield JD. Nucleotide diversity is a poor predictor of short-term adaptive potential. Proc Natl Acad Sci U S A. 2026;123(27):e2536181123. doi:10.1073/pnas.2536181123 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/nucleotide-diversity-poor-predictor-adaptive-potential QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-08. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript's coverage of core scientific claims: relationship between π and IA, the π vs He relationship, functional variation (πN/πS), the theoretical basis (stabilizing selection), and conservation implications/policy directions. - transcript topics: Adaptive potential and evolvability (IA) concept; Nucleotide diversity (π) as predictor of evolvability; Microsatellite diversity (He) and its relation to π and IA; Theoretical mutation–selection...

  8. 7. Juli

    409: A systems-level atlas of carbon-response transcriptional states in Escherichia coli

    Shin J et al., PNAS - This episode examines a large transcriptome compendium (PRECISE-NP881) that profiles E. coli K-12 MG1655 across 43 carbon substrates. Independent component analysis resolved 137 iModulons, including 25 carbon-catabolism modules that organize substrates into four activity-defined groups tied to growth rate, substrate chemistry, metabolic entry routes, and proteome allocation. The study integrates growth phenotyping, FBA/ME-modeling, targeted knockouts, and reanalysis of a starvation/refeeding time course to connect transcriptional modules to physiological context. Key terms: carbon response, iModulon, Escherichia coli, carbon catabolite repression, transcriptional regulatory network. Study Highlights: The authors assembled PRECISE-NP881 (881 transcriptomes) and used ICA to define 137 iModulons, 25 of which are carbon-catabolism modules whose activities cluster substrates into four groups. Faster-growing sugars showed limited CRP-linked remodeling while slower-growth, non-glycolytic substrates activated CRP-linked, NtrC-1, Propionate, and SgcABCEQX iModulons. Targeted knockouts (e.g., ΔprpC) demonstrated conditional growth defects on Group C/D substrates supporting a role for methylcitrate-mediated propionyl-CoA processing. Proteome-allocation modeling and projection of an independent starvation/refeeding dataset corroborated links between carbon-response modules, growth/stress physiology, and metabolite dynamics. Conclusion: The paper provides a quantitative atlas of carbon-responsive transcriptional states in E. coli, decomposing CCR into separable CRP-linked and substrate-specific modules and linking these modules to growth rate, metabolic context, proteome allocation, and conditional physiological relevance. Music: Enjoy the music based on this article at the end of the episode. Article title: A systems-level atlas of carbon-response transcriptional states in Escherichia coli First author: Shin J Journal: PNAS DOI: 10.1073/pnas.2531884123 Reference: Shin J, Son HF, Krishnan J, Hefner Y, Szubin R, Sung J, Patel A, Lou XA, Catoiu EA, Palsson BØ, Zielinski DC. A systems-level atlas of carbon-response transcriptional states in Escherichia coli. PNAS. 2026;123(27):e2531884123. doi:10.1073/pnas.2531884123. 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 is independent and ad-free — no sponsors, no paywall. If an episode was worth your time, chip in and keep the papers audited and the original songs coming: ❤️ Support monthly: https://buy.stripe.com/cNifZhclVebvagk2JDgEg01 ☕ One-time donation: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 More at 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/atlas-carbon-response-transcriptional-states-e-coli QC: This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-07. QC Scope: - article metadata and core scientific claims from the narration - excludes analogies, intro/outro, and music - transcript coverage: Audited the transcript sections describing PRECISE-NP881 atlas construction ( ICA/iModulons ), four substrate groups (A–D), CRP decomposition into Crp-1/Crp-2/Crp-3, NtrC-1 and Propionate iModulons linked to propionyl-CoA stress, methylcitrate pathway (prpC/astC), SgcABCEQX prophage iModulon, starvation/refeeding dynam - transcript topics: ICA-based iModulon analysis; CRP-linked iModulons decomposition (Crp-1, Crp-2, Crp-3); Four substrate groups (A–D) and growth phenotypes; NtrC-1 and Propiona...

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Base by Base explores advances in genetics and genomics, with a focus on gene-disease associations, variant interpretation, protein structure, and insights from exome and genome sequencing. Each episode breaks down key studies and their clinical relevance—one base at a time. Powered by AI, Base by Base offers a new way to learn on the go. Special thanks to authors who publish under CC BY 4.0, making open-access science faster to share and easier to explore.

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  • Erstellt von
    Gustavo Barra
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    2025 - 2026
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