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Browse the failure-mode index

473 real negative results, null findings, and replication failures in Biochemistry, Genetics and Molecular Biology. Search the index →

WASTE indexes published research — it does not host or republish full papers. Each entry is a metadata record compiled from open scholarly databases; the abstract is shown in full only where the paper is openly licensed, otherwise a short excerpt under fair use. Classifications are automated and approximate.

Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Directed Evolution Pipeline for the Improvement of Orthogonal Translation Machinery for Genetic Code Expansion at Sense Codons

Wil Biddle, David G. Schwark, Margaret A. Schmitt et al. · 2022 · Frontiers in Chemistry

The expansion of the genetic code beyond a single type of noncanonical amino acid (ncAA) is hindered by inefficient machinery for reassigning the meaning of sense codons. A major obstacle to using directed evolution to improve the efficiency of sense codon reassignment is that fractional sense codon reassignments lead to heterogeneous mixtures of full-length proteins with either a ncAA or a natural amino acid incorporated in response to the targeted codon. In stop codon suppression systems, missed incorporations lead to truncated proteins; improvements in activity may be inferred from increase

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Artificial Intelligence for Exosomal Biomarker Discovery for Cardiovascular Diseases: Multi-Omics Integration, Reproducibility, and Translational Prospects

Rasit Dinc, Nurittin Ardıç · 2026 · Cells

Exosomes and other extracellular vesicles (EVs) carry microRNAs, proteins, and lipids that reflect cardiovascular pathophysiology and can enable minimally invasive biomarker discovery. However, EV datasets are highly dimensional and heterogeneous, strongly influenced by pre-analytic variables and non-standardized isolation/characterization workflows, limiting reproducibility across studies. Artificial intelligence (AI), including machine learning (ML), deep learning (DL), and network-based approaches, can support EV biomarker development by integrating multi-omics profiles with clinical metada

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Failed Experiment ReportOpen accessBiochemistry, Genetics and Molecular Biology

A Francisella tularensis Live Vaccine Strain That Improves Stimulation of Antigen-Presenting Cells Does Not Enhance Vaccine Efficacy

Deanna Schmitt, Dawn M. O’Dee, Joseph Horzempa et al. · 2012 · PLoS ONE

Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS), does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetical

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Fusing metabolomics data sets with heterogeneous measurement errors

Sandra Waaijenborg, Oksana Korobko, Ko Willems van Dijk et al. · 2018 · PLoS ONE

Combining different metabolomics platforms can contribute significantly to the discovery of complementary processes expressed under different conditions. However, analysing the fused data might be hampered by the difference in their quality. In metabolomics data, one often observes that measurement errors increase with increasing measurement level and that different platforms have different measurement error variance. In this paper we compare three different approaches to correct for the measurement error heterogeneity, by transformation of the raw data, by weighted filtering before modelling

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Population Levels Assessment of the Distribution of Disease-Associated Variants With Emphasis on Armenians – A Machine Learning Approach

Maria Nikogհosyan, Siras Hakobyan, Anahit Hovhannisyan et al. · 2019 · Frontiers in Genetics

Background: During last decades a number of genome-wide association studies (GWAS) has identified numerous single nucleotide polymorphisms (SNPs) associated with different complex diseases. However, associations reported in one population are often conflicting and did not replicate when studied in other populations. One of the reasons could be that most of GWAS employ case-control design in one or a limited number of populations, but little attention was paid to global distribution of disease associated alleles across different populations. Moreover, the majority of GWAS have been performed on

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0–1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database

Guangfu Hu, Guangxia Hu, Chengjiao Zhang et al. · 2020 · BMC Cancer

BACKGROUND: The benefit of adjuvant chemotherapy in invasive lobular carcinoma (ILC) is still unclear. The objective of the current study was to elucidate the effectiveness of adjuvant chemotherapy in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1b-c/N0-1/M0 ILC. METHODS: Based on Surveillance, Epidemiology, and End-Results (SEER) database, we identified original 12,334 HR-positive, HER2-negative, pT1b-c/N0-1/M0 ILC patients, who were then divided into adjuvant chemotherapy group and control group. End-points were overall survival (OS) and breast

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Mutualism breakdown underpins evolutionary rescue in an obligate cross-feeding bacterial consortium

Ignacio J. Melero‐Jiménez, Yael Sorokin, Ami Merlin et al. · 2025 · Nature Communications

Populations facing lethal environmental change can escape extinction through rapid genetic adaptation, a process known as evolutionary rescue. Despite extensive study, evolutionary rescue is largely unexplored in mutualistic communities, where it is likely constrained by the less adaptable partner. Here, we explored empirically the likelihood, population dynamics, and genetic mechanisms underpinning evolutionary rescue in an obligate mutualism involving cross-feeding of amino acids between auxotrophic Escherichia coli strains. We found that over 80% of populations overcame a severe decline whe

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The HDAC inhibitor romidepsin renders liver cancer vulnerable to RTK targeting and immunologically active

Celia Sequera, Margherita Grattarola, Floriane Cannet et al. · 2025 · Nature Communications

Histone deacetylases (HDACs) are epigenetic regulators frequently altered in cancer. Here we report that overexpression of HDAC1/2 occurs in Hepatocellular Carcinoma (HCC) patients, correlating with poor prognosis. We show that romidepsin,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Microbial diversification is maintained in an experimentally evolved synthetic community

Zahraa S. Al-tameemi, Alejandra Rodríguez‐Verdugo · 2024 · mSystems

ABSTRACT Microbial communities are incredibly diverse. Yet, the eco-evolutionary processes originating and maintaining this diversity remain understudied. Here, we investigate the patterns of diversification for Pseudomonas putida evolving in isolation and with Acinetobacter johnsonii leaking resources used by P. putida . We experimentally evolved four experimental replicates in monoculture and co-culture for 200 generations. We observed that P. putida diversified into two distinct morphotypes that differed from their ancestor by single-point mutations. One of the most prominent mutations hit

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

CRISPR–Cas technologies in neurodegenerative disorders: mechanistic insights, therapeutic potential, and translational challenges

Raya Kh. Yashooa, Ari Q. Nabi, Shukur Wasman Smail et al. · 2026 · Frontiers in Neurology

CRISPR-Cas genome-editing technologies have emerged as powerful tools for precise DNA and RNA modulation, offering promising therapeutic strategies for neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This review critically evaluates current CRISPR/Cas applications in neurodegeneration, with emphasis on mechanistic insights, therapeutic outcomes, and translational feasibility. Preclinical and early translational studies demonstrate that CRISPR-Cas platforms can correct pathogenic mutation

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Genome-wide association study identifies common variants associated with breast cancer in South African Black women

M Hayat, Wenlong Carl Chen, Chantal Babb de Villiers et al. · 2025 · Nature Communications

Abstract Genome-wide association studies (GWAS) have characterized the contribution of common variants to breast cancer (BC) risk in populations of European ancestry, however GWAS have not been reported in resident African populations. This GWAS included 2485 resident African BC cases and 1101 population matched controls. Two risk loci were identified, located between UNC13C and RAB27A on chromosome 15 (rs7181788, p = 1.01 × 10 −08 ) and in USP22 on chromosome 17 (rs899342, p = 4.62 × 10 −08 ). Several genome-wide significant signals were also detected in hormone receptor subtype analysis. The

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Diagnosis value of targeted and metagenomic sequencing in respiratory tract infection

Yukun Kuang, Weiping Tan, Chaohui Hu et al. · 2024 · Frontiers in Cellular and Infection Microbiology

Background: Targeted next-generation sequencing (tNGS) has become a trending tool in the field of infection diagnosis, but concerns are also raising about its performance compared with metagenomic next-generation sequencing (mNGS). This study aims to explore the clinical feasibility of a tNGS panel for respiratory tract infection diagnosis and compare it with mNGS in the same cohort of inpatients. Methods: 180 bronchoalveolar lavage fluid samples were collected and sent to two centers for mNGS and tNGS blinded tests, respectively. The concordance between pathogen reports of both methods and th

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Impact of transfer learning methods and dataset characteristics on generalization in birdsong classification

Burooj Ghani, Vincent J. Kalkman, Bob Planqué et al. · 2025 · Scientific Reports

Animal sounds can be recognised automatically by machine learning, and this has an important role to play in biodiversity monitoring. Yet despite increasingly impressive capabilities, bioacoustic species classifiers still exhibit imbalanced performance across species and habitats, especially in complex soundscapes. In this study, we explore the effectiveness of transfer learning in large-scale bird sound classification across various conditions, including single- and multi-label scenarios, and across different model architectures such as CNNs and Transformers. Our experiments demonstrate that

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

PRKCZmethylation is associated with sunlight exposure in a North American but not a Mediterranean population

Stella Aslibekyan, Hassan S. Dashti, Toshiko Tanaka et al. · 2014 · Chronobiology International

Sunlight exposure has been shown to alter DNA methylation patterns across several human cell-types, including T-lymphocytes. Since epigenetic changes establish gene expression profiles, changes in DNA methylation induced by sunlight…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Identifying statistically significant combinatorial markers for survival analysis

Raissa Relator, Aika Terada, Jun Sese · 2018 · BMC Medical Genomics

BACKGROUND: Survival analysis methods have been widely applied in different areas of health and medicine, spanning over varying events of interest and target diseases. They can be utilized to provide relationships between the survival time of individuals and factors of interest, rendering them useful in searching for biomarkers in diseases such as cancer. However, some disease progression can be very unpredictable because the conventional approaches have failed to consider multiple-marker interactions. An exponential increase in the number of candidate markers requires large correction factor

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Negative / Null Result ReportBiochemistry, Genetics and Molecular Biology

Glycomacromolecules to Tailor Crowded and Heteromultivalent Glycocalyx Mimetics

Luca‐Cesare Blawitzki, Nina Bartels, Lorand Bonda et al. · 2024 · Biomacromolecules

The glycocalyx, a complex carbohydrate layer on cell surfaces, plays a crucial role in various biological processes. Understanding native glycocalyces' complexity is challenging due to their intricate and dynamic nature. Simplified mimics…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

New cycle, same old mistakes? Overlapping vs. discrete generations in long-term recurrent selection

Marlee R. Labroo, Jessica Rutkoski · 2022 · BMC Genomics

BACKGROUND: Recurrent selection is a foundational breeding method for quantitative trait improvement. It typically features rapid breeding cycles that can lead to high rates of genetic gain. Usually, generations are discrete in recurrent selection, which means that breeding candidates are evaluated and considered for selection for only one cycle. Alternately, generations can overlap, with breeding candidates considered for selection as parents for multiple cycles. With recurrent genomic selection but not phenotypic selection, candidates can be re-evaluated by using genomic estimated breeding v

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Mitochondrial Dysfunction in Cardiomyopathy and Heart Failure: From Energetic Collapse to Therapeutic Opportunity

Nikola Pavlović, Petar Todorović, Mirko Maglica et al. · 2025 · Biomolecules

The heart’s relentless contractile activity depends critically on mitochondrial function to meet its extraordinary bioenergetic demands. Mitochondria, through oxidative phosphorylation, not only supply ATP but also regulate metabolism, calcium homeostasis, and apoptotic signaling, ensuring cardiomyocyte viability and cardiac function. Mitochondrial dysfunction is a hallmark of cardiomyopathies and heart failure, characterized by impaired oxidative phosphorylation, excessive production of reactive oxygen species (ROS), dysregulated calcium handling, and disturbances in mitochondrial dynamics an

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

De novo and inherited dominant variants in U4 and U6 snRNA genes cause retinitis pigmentosa

Mathieu Quinodoz, Kim Rodenburg, Zuzana Cvačková et al. · 2026 · Nature Genetics

Small nuclear RNAs (snRNAs) combine with specific proteins to generate small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. U4 snRNA forms a duplex with U6 and, together with U5, contributes to the tri-snRNP…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

When to Trust Epigenetic Clocks: Avoiding False Positives in Aging Interventions

Daniel S. Borrus, Raghav Sehgal, Judith Armstrong et al. · 2026 · Aging Cell

ABSTRACT Epigenetic clocks have emerged as potential biomarkers of aging due to their association with morbidity and mortality. They have recently gained traction as outcome measurements for anti‐aging interventions. However, as the number of new epigenetic clocks continues to grow, different clocks may not agree on the effect of an intervention. This raises the question of when researchers can trust epigenetic clock results. In this study, we find that when extending previously published single‐clock intervention studies to include additional clock models, no additional clocks reach statistic

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Non-standard proteins in the lens of AlphaFold 3: a case study of amyloids

Alicja W. Wojciechowska, Jakub W. Wojciechowski, Gert Vriend et al. · 2026 · Scientific Reports

Abstract While three-dimensional structures of globular and transmembrane forms are available for many amyloid proteins, structures of their amyloid forms are scarce in the PDB. Amyloids pose major challenges for both experimental…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Factors correlating with significant differences between X-ray structures of myoglobin

Alexander A. Rashin, Marcin J. Domagalski, Michael T. Zimmermann et al. · 2014 · Acta Crystallographica Section D Biological Crystallography

Validation of general ideas about the origins of conformational differences in proteins is critical in order to arrive at meaningful functional insights. Here, principal component analysis (PCA) and distance difference matrices are used to…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of Gαqprotein-induced cardiomyopathy

Valeriy Timofeyev, C. A. Porter, Dipika Tuteja et al. · 2010 · American Journal of Physiology-Heart and Circulatory Physiology

Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC(V) and AC(VI) are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Complex trait methylation scores in the prediction of major depressive disorder

Miruna C. Barbu, Carmen Amador, Alex S. F. Kwong et al. · 2022 · EBioMedicine

BACKGROUND: DNA methylation (DNAm) is associated with time-varying environmental factors that contribute to major depressive disorder (MDD) risk. We sought to test whether DNAm signatures of lifestyle and biochemical factors were associated with MDD to reveal dynamic biomarkers of MDD risk that may be amenable to lifestyle interventions. METHODS: , N=565), using CpG sites reported in previous well-powered methylome-wide association studies. We also compared their predictive accuracy for MDD to a MDD MS in an independent GS sub-sample (N=4,432). FINDINGS: =-0.069-0.083) remained significantly a

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

A genome-wide association study of mass spectrometry proteomics using a nanoparticle enrichment platform

Karsten Suhre, Qingwen Chen, Anna Halama et al. · 2025 · Nature Genetics

Most studies to date of protein quantitative trait loci (pQTLs) have relied on affinity proteomics platforms, which provide only limited information about the targeted protein isoforms and may be affected by genetic variation in their epitope binding. Here we show that mass spectrometry (MS)-based proteomics can complement these studies and provide insights into the role of specific protein isoform and epitope-altering variants. Using the Seer Proteograph nanoparticle enrichment MS platform, we identified and replicated new pQTLs in a genome-wide association study of proteins in blood plasma s

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

The Road to Remyelination in Multiple Sclerosis: Breakthroughs, Challenges, and Considerations for Future Trial Design

Leah Zuroff, Vista Farkhondeh, Riley Bove et al. · 2025 · Drugs

Despite major advances in multiple sclerosis (MS) treatment, disability accumulation independent of relapse activity remains a significant challenge. Chronic demyelination is a key driver of neurodegeneration and disease progression,…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Gut microbial metabolites in inflammatory bowel disease: immunological mechanisms regulating Treg/Th17 balance and therapeutic potential

He Chen, Shaochen Yu, Mengjie Zhang et al. · 2026 · Frontiers in Immunology

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder resulting from a combination of genetic susceptibility, environmental factors, and an abnormal immune response of the intestinal immune system to commensal microorganisms. The gut microbiota and its metabolites play a pivotal role in maintaining intestinal immune homeostasis. Recent advances indicate that dysbiosis of the microbiota is accompanied by alterations in its metabolic functions. Abnormal levels of key metabolites, particularly short-chain fatty acids (SCFAs), tryptophan derivatives, and secondary bile acids, are clo

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Tetanus in the Elderly: The Management of Intensive Care and Prolonged Hospitalization

Hiroki Isono, Taiju Miyagami, Kohta Katayama et al. · 2016 · Internal Medicine

Tetanus is a potentially fatal infection. Approximately 100 cases are reported in Japan each year; however, little is known about its clinical course and outcomes in the current era of treatment. We herein report three cases of tetanus in…

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Anticancer efficacy of the hypoxia‐activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma

Vasilios Liapis, Aneta Zysk, Mark DeNichilo et al. · 2017 · Cancer Medicine

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in

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Negative / Null Result ReportOpen accessBiochemistry, Genetics and Molecular Biology

Ex vivo infection model for Francisella using human lung tissue

Kristin Köppen, Diana Fatykhova, Gudrun Holland et al. · 2023 · Frontiers in Cellular and Infection Microbiology

Introduction Tularemia is mainly caused by Francisella tularensis ( Ft ) subsp. tularensis ( Ftt ) and Ft subsp. holarctica ( Ftt ) in humans and in more than 200 animal species including rabbits and hares. Human clinical manifestations depend on the route of infection and range from flu-like symptoms to severe pneumonia with a mortality rate up to 60% without treatment. So far, only 2D cell culture and animal models are used to study Francisella virulence , but the gained results are transferable to human infections only to a certain extent. Method In this study, we firstly established an ex

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