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1.
Proc Natl Acad Sci U S A ; 121(25): e2320066121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38861605

RESUMEN

How are the merits of innovative ideas communicated in science? Here, we conduct semantic analyses of grant application success with a focus on scientific promotional language, which may help to convey an innovative idea's originality and significance. Our analysis attempts to surmount the limitations of prior grant studies by examining the full text of tens of thousands of both funded and unfunded grants from three leading public and private funding agencies: the NIH, the NSF, and the Novo Nordisk Foundation, one of the world's largest private science funding foundations. We find a robust association between promotional language and the support and adoption of innovative ideas by funders and other scientists. First, a grant proposal's percentage of promotional language is associated with up to a doubling of the grant's probability of being funded. Second, a grant's promotional language reflects its intrinsic innovativeness. Third, the percentage of promotional language is predictive of the expected citation and productivity impact of publications that are supported by funded grants. Finally, a computer-assisted experiment that manipulates the promotional language in our data demonstrates how promotional language can communicate the merit of ideas through cognitive activation. With the incidence of promotional language in science steeply rising, and the pivotal role of grants in converting promising and aspirational ideas into solutions, our analysis provides empirical evidence that promotional language is associated with effectively communicating the merits of innovative scientific ideas.


Asunto(s)
Lenguaje , Humanos , Ciencia , Organización de la Financiación , Estados Unidos , Apoyo a la Investigación como Asunto , Creatividad
2.
Proc Natl Acad Sci U S A ; 121(38): e2322764121, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39250662

RESUMEN

Are members of marginalized communities silenced on social media when they share personal experiences of racism? Here, we investigate the role of algorithms, humans, and platform guidelines in suppressing disclosures of racial discrimination. In a field study of actual posts from a neighborhood-based social media platform, we find that when users talk about their experiences as targets of racism, their posts are disproportionately flagged for removal as toxic by five widely used moderation algorithms from major online platforms, including the most recent large language models. We show that human users disproportionately flag these disclosures for removal as well. Next, in a follow-up experiment, we demonstrate that merely witnessing such suppression negatively influences how Black Americans view the community and their place in it. Finally, to address these challenges to equity and inclusion in online spaces, we introduce a mitigation strategy: a guideline-reframing intervention that is effective at reducing silencing behavior across the political spectrum.


Asunto(s)
Racismo , Medios de Comunicación Sociales , Humanos , Negro o Afroamericano , Algoritmos
3.
Am J Hum Genet ; 110(10): 1661-1672, 2023 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-37741276

RESUMEN

In the effort to treat Mendelian disorders, correcting the underlying molecular imbalance may be more effective than symptomatic treatment. Identifying treatments that might accomplish this goal requires extensive and up-to-date knowledge of molecular pathways-including drug-gene and gene-gene relationships. To address this challenge, we present "parsing modifiers via article annotations" (PARMESAN), a computational tool that searches PubMed and PubMed Central for information to assemble these relationships into a central knowledge base. PARMESAN then predicts putatively novel drug-gene relationships, assigning an evidence-based score to each prediction. We compare PARMESAN's drug-gene predictions to all of the drug-gene relationships displayed by the Drug-Gene Interaction Database (DGIdb) and show that higher-scoring relationship predictions are more likely to match the directionality (up- versus down-regulation) indicated by this database. PARMESAN had more than 200,000 drug predictions scoring above 8 (as one example cutoff), for more than 3,700 genes. Among these predicted relationships, 210 were registered in DGIdb and 201 (96%) had matching directionality. This publicly available tool provides an automated way to prioritize drug screens to target the most-promising drugs to test, thereby saving time and resources in the development of therapeutics for genetic disorders.


Asunto(s)
PubMed , Humanos , Bases de Datos Factuales
4.
Proc Natl Acad Sci U S A ; 120(39): e2304513120, 2023 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-37725643

RESUMEN

Nitrate supply is fundamental to support shoot growth and crop performance, but the associated increase in stem height exacerbates the risks of lodging and yield losses. Despite their significance for agriculture, the mechanisms involved in the promotion of stem growth by nitrate remain poorly understood. Here, we show that the elongation of the hypocotyl of Arabidopsis thaliana, used as a model, responds rapidly and persistently to upshifts in nitrate concentration, rather than to the nitrate level itself. The response occurred even in shoots dissected from their roots and required NITRATE TRANSPORTER 1.1 (NRT1.1) in the phosphorylated state (but not NRT1.1 nitrate transport capacity) and NIN-LIKE PROTEIN 7 (NLP7). Nitrate increased PHYTOCHROME INTERACTING FACTOR 4 (PIF4) nuclear abundance by posttranscriptional mechanisms that depended on NRT1.1 and phytochrome B. In response to nitrate, PIF4 enhanced the expression of numerous SMALL AUXIN-UP RNA (SAUR) genes in the hypocotyl. The growth response to nitrate required PIF4, positive and negative regulators of its activity, including AUXIN RESPONSE FACTORs, and SAURs. PIF4 integrates cues from the soil (nitrate) and aerial (shade) environments adjusting plant stature to facilitate access to light.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Fitocromo , Nitratos/farmacología , Fitocromo B , Arabidopsis/genética , Ácidos Indolacéticos , Transportadores de Nitrato , ARN , Proteínas de Arabidopsis/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética
5.
Proc Natl Acad Sci U S A ; 120(23): e2216162120, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37253013

RESUMEN

Across the United States, police chiefs, city officials, and community leaders alike have highlighted the need to de-escalate police encounters with the public. This concern about escalation extends from encounters involving use of force to routine car stops, where Black drivers are disproportionately pulled over. Yet, despite the calls for action, we know little about the trajectory of police stops or how escalation unfolds. In study 1, we use methods from computational linguistics to analyze police body-worn camera footage from 577 stops of Black drivers. We find that stops with escalated outcomes (those ending in arrest, handcuffing, or a search) diverge from stops without these outcomes in their earliest moments-even in the first 45 words spoken by the officer. In stops that result in escalation, officers are more likely to issue commands as their opening words to the driver and less likely to tell drivers the reason why they are being stopped. In study 2, we expose Black males to audio clips of the same stops and find differences in how escalated stops are perceived: Participants report more negative emotion, appraise officers more negatively, worry about force being used, and predict worse outcomes after hearing only the officer's initial words in escalated versus non-escalated stops. Our findings show that car stops that end in escalated outcomes sometimes begin in an escalated fashion, with adverse effects for Black male drivers and, in turn, police-community relations.


Asunto(s)
Negro o Afroamericano , Aplicación de la Ley , Policia , Humanos , Masculino , Aplicación de la Ley/métodos , Estados Unidos , Racismo , Emociones
6.
Plant J ; 119(1): 266-282, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38605581

RESUMEN

Brassica crops are susceptible to diseases which can be mitigated by breeding for resistance. MAMPs (microbe-associated molecular patterns) are conserved molecules of pathogens that elicit host defences known as pattern-triggered immunity (PTI). Necrosis and Ethylene-inducing peptide 1-like proteins (NLPs) are MAMPs found in a wide range of phytopathogens. We studied the response to BcNEP2, a representative NLP from Botrytis cinerea, and showed that it contributes to disease resistance in Brassica napus. To map regions conferring NLP response, we used the production of reactive oxygen species (ROS) induced during PTI across a population of diverse B. napus accessions for associative transcriptomics (AT), and bulk segregant analysis (BSA) on DNA pools created from a cross of NLP-responsive and non-responsive lines. In silico mapping with AT identified two peaks for NLP responsiveness on chromosomes A04 and C05 whereas the BSA identified one peak on A04. BSA delimited the region for NLP-responsiveness to 3 Mbp, containing ~245 genes on the Darmor-bzh reference genome and four co-segregating KASP markers were identified. The same pipeline with the ZS11 genome confirmed the highest-associated region on chromosome A04. Comparative BLAST analysis revealed unannotated clusters of receptor-like protein (RLP) homologues on ZS11 chromosome A04. However, no specific RLP homologue conferring NLP response could be identified. Our results also suggest that BR-SIGNALLING KINASE1 may be involved with modulating the NLP response. Overall, we demonstrate that responsiveness to NLP contributes to disease resistance in B. napus and define the associated genomic location. These results can have practical application in crop improvement.


Asunto(s)
Brassica napus , Resistencia a la Enfermedad , Enfermedades de las Plantas , Proteínas de Plantas , Brassica napus/genética , Brassica napus/microbiología , Brassica napus/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Resistencia a la Enfermedad/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Botrytis/fisiología , Especies Reactivas de Oxígeno/metabolismo , Péptidos/metabolismo , Péptidos/genética , Regulación de la Expresión Génica de las Plantas , Mapeo Cromosómico , Etilenos/metabolismo
7.
Brief Bioinform ; 24(5)2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37478371

RESUMEN

Artificial intelligence (AI) systems utilizing deep neural networks and machine learning (ML) algorithms are widely used for solving critical problems in bioinformatics, biomedical informatics and precision medicine. However, complex ML models that are often perceived as opaque and black-box methods make it difficult to understand the reasoning behind their decisions. This lack of transparency can be a challenge for both end-users and decision-makers, as well as AI developers. In sensitive areas such as healthcare, explainability and accountability are not only desirable properties but also legally required for AI systems that can have a significant impact on human lives. Fairness is another growing concern, as algorithmic decisions should not show bias or discrimination towards certain groups or individuals based on sensitive attributes. Explainable AI (XAI) aims to overcome the opaqueness of black-box models and to provide transparency in how AI systems make decisions. Interpretable ML models can explain how they make predictions and identify factors that influence their outcomes. However, the majority of the state-of-the-art interpretable ML methods are domain-agnostic and have evolved from fields such as computer vision, automated reasoning or statistics, making direct application to bioinformatics problems challenging without customization and domain adaptation. In this paper, we discuss the importance of explainability and algorithmic transparency in the context of bioinformatics. We provide an overview of model-specific and model-agnostic interpretable ML methods and tools and outline their potential limitations. We discuss how existing interpretable ML methods can be customized and fit to bioinformatics research problems. Further, through case studies in bioimaging, cancer genomics and text mining, we demonstrate how XAI methods can improve transparency and decision fairness. Our review aims at providing valuable insights and serving as a starting point for researchers wanting to enhance explainability and decision transparency while solving bioinformatics problems. GitHub: https://github.com/rezacsedu/XAI-for-bioinformatics.


Asunto(s)
Inteligencia Artificial , Biología Computacional , Humanos , Aprendizaje Automático , Algoritmos , Genómica
8.
Brief Bioinform ; 24(3)2023 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-37165972

RESUMEN

MicroRNAs are small regulatory RNAs that decrease gene expression after transcription in various biological disciplines. In bioinformatics, identifying microRNAs and predicting their functionalities is critical. Finding motifs is one of the most well-known and important methods for identifying the functionalities of microRNAs. Several motif discovery techniques have been proposed, some of which rely on artificial intelligence-based techniques. However, in the case of few or no training data, their accuracy is low. In this research, we propose a new computational approach, called DiMo, for identifying motifs in microRNAs and generally macromolecules of small length. We employ word embedding techniques and deep learning models to improve the accuracy of motif discovery results. Also, we rely on transfer learning models to pre-train a model and use it in cases of a lack of (enough) training data. We compare our approach with five state-of-the-art works using three real-world datasets. DiMo outperforms the selected related works in terms of precision, recall, accuracy and f1-score.


Asunto(s)
Aprendizaje Profundo , MicroARNs , MicroARNs/genética , Inteligencia Artificial , Algoritmos
9.
Brief Bioinform ; 24(6)2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37864295

RESUMEN

The widespread adoption of high-throughput omics technologies has exponentially increased the amount of protein sequence data involved in many salient disease pathways and their respective therapeutics and diagnostics. Despite the availability of large-scale sequence data, the lack of experimental fitness annotations underpins the need for self-supervised and unsupervised machine learning (ML) methods. These techniques leverage the meaningful features encoded in abundant unlabeled sequences to accomplish complex protein engineering tasks. Proficiency in the rapidly evolving fields of protein engineering and generative AI is required to realize the full potential of ML models as a tool for protein fitness landscape navigation. Here, we support this work by (i) providing an overview of the architecture and mathematical details of the most successful ML models applicable to sequence data (e.g. variational autoencoders, autoregressive models, generative adversarial neural networks, and diffusion models), (ii) guiding how to effectively implement these models on protein sequence data to predict fitness or generate high-fitness sequences and (iii) highlighting several successful studies that implement these techniques in protein engineering (from paratope regions and subcellular localization prediction to high-fitness sequences and protein design rules generation). By providing a comprehensive survey of model details, novel architecture developments, comparisons of model applications, and current challenges, this study intends to provide structured guidance and robust framework for delivering a prospective outlook in the ML-driven protein engineering field.


Asunto(s)
Redes Neurales de la Computación , Aprendizaje Automático no Supervisado , Secuencia de Aminoácidos , Ejercicio Físico , Proteínas/genética
10.
BMC Bioinformatics ; 25(1): 84, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413851

RESUMEN

BACKGROUND: Thousands of genes have been associated with different Mendelian conditions. One of the valuable sources to track these gene-disease associations (GDAs) is the Online Mendelian Inheritance in Man (OMIM) database. However, most of the information in OMIM is textual, and heterogeneous (e.g. summarized by different experts), which complicates automated reading and understanding of the data. Here, we used Natural Language Processing (NLP) to make a tool (Gene-Phenotype Association Discovery (GPAD)) that could syntactically process OMIM text and extract the data of interest. RESULTS: GPAD applies a series of language-based techniques to the text obtained from OMIM API to extract GDA discovery-related information. GPAD can inform when a particular gene was associated with a specific phenotype, as well as the type of validation-whether through model organisms or cohort-based patient-matching approaches-for such an association. GPAD extracted data was validated with published reports and was compared with large language model. Utilizing GPAD's extracted data, we analysed trends in GDA discoveries, noting a significant increase in their rate after the introduction of exome sequencing, rising from an average of about 150-250 discoveries each year. Contrary to hopes of resolving most GDAs for Mendelian disorders by now, our data indicate a substantial decline in discovery rates over the past five years (2017-2022). This decline appears to be linked to the increasing necessity for larger cohorts to substantiate GDAs. The rising use of zebrafish and Drosophila as model organisms in providing evidential support for GDAs is also observed. CONCLUSIONS: GPAD's real-time analyzing capacity offers an up-to-date view of GDA discovery and could help in planning and managing the research strategies. In future, this solution can be extended or modified to capture other information in OMIM and scientific literature.


Asunto(s)
Procesamiento de Lenguaje Natural , Pez Cebra , Humanos , Animales , Fenotipo , Bases de Datos Genéticas , Predicción
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