scholarly journals Deciphering the language of antibodies using self-supervised learning

2021 ◽  
Author(s):  
Jinwoo Leem ◽  
Laura Sophie Mitchell ◽  
James Henry Royston Farmery ◽  
Justin Barton ◽  
Jacob Daniel Galson

An individual's B cell receptor (BCR) repertoire encodes information about past immune responses, and potential for future disease protection. Deciphering the information stored in BCR sequence datasets will transform our fundamental understanding of disease and enable discovery of novel diagnostics and antibody therapeutics. One of the grand challenges of BCR sequence analysis is the prediction of BCR properties from their amino acid sequence alone. Here we present an antibody-specific language model, AntiBERTa, which provides a contextualised representation of BCR sequences. Following pre-training, we show that AntiBERTa embeddings learn biologically relevant information, generalizable to a range of applications. As a case study, we demonstrate how AntiBERTa can be fine-tuned to predict paratope positions from an antibody sequence, outperforming public tools across multiple metrics. To our knowledge, AntiBERTa is the deepest protein family-specific language model, providing a rich representation of BCRs. AntiBERTa embeddings are primed for multiple downstream tasks and can improve our understanding of the language of antibodies.

2020 ◽  
pp. jbc.RA120.016511
Author(s):  
Seung J Kim ◽  
James I MacDonald ◽  
Frederick A. Dick

The retinoblastoma tumour suppressor protein (RB) plays an important role in biological processes such as cell cycle control, DNA damage repair, epigenetic regulation, and genome stability. The canonical model of RB regulation is that cyclin-CDKs phosphorylate, and render RB inactive in late G1/S, promoting entry into S phase. Recently, mono-phosphorylated RB species were described to have distinct cell-cycle independent functions, suggesting that a phosphorylation code dictates diversity of RB function. However, a biologically relevant, functional role of RB phosphorylation at non-CDK sites has remained elusive. Here, we investigated S838/T841 dual phosphorylation, its upstream stimulus, and downstream functional output.  We found that mimicking T-cell receptor activation in Jurkat leukemia cells induced sequential activation of downstream kinases including p38 MAPK, and RB S838/T841 phosphorylation.  This signaling pathway disrupts RB and condensin II interaction with chromatin.  Using cells expressing a WT or S838A/T841A mutant RB fragment, we present evidence that deficiency for this phosphorylation event prevents condensin II release from chromatin.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gulden Olgun ◽  
Afshan Nabi ◽  
Oznur Tastan

Abstract Background While some non-coding RNAs (ncRNAs) are assigned critical regulatory roles, most remain functionally uncharacterized. This presents a challenge whenever an interesting set of ncRNAs needs to be analyzed in a functional context. Transcripts located close-by on the genome are often regulated together. This genomic proximity on the sequence can hint at a functional association. Results We present a tool, NoRCE, that performs cis enrichment analysis for a given set of ncRNAs. Enrichment is carried out using the functional annotations of the coding genes located proximal to the input ncRNAs. Other biologically relevant information such as topologically associating domain (TAD) boundaries, co-expression patterns, and miRNA target prediction information can be incorporated to conduct a richer enrichment analysis. To this end, NoRCE includes several relevant datasets as part of its data repository, including cell-line specific TAD boundaries, functional gene sets, and expression data for coding & ncRNAs specific to cancer. Additionally, the users can utilize custom data files in their investigation. Enrichment results can be retrieved in a tabular format or visualized in several different ways. NoRCE is currently available for the following species: human, mouse, rat, zebrafish, fruit fly, worm, and yeast. Conclusions NoRCE is a platform-independent, user-friendly, comprehensive R package that can be used to gain insight into the functional importance of a list of ncRNAs of any type. The tool offers flexibility to conduct the users’ preferred set of analyses by designing their own pipeline of analysis. NoRCE is available in Bioconductor and https://github.com/guldenolgun/NoRCE.


2021 ◽  
Vol 13 (8) ◽  
pp. 4186
Author(s):  
Abdulhakeem Raji ◽  
Abeer Hassan

This paper adopted a case study approach to investigate the sustainability practices of a Scottish university in order to understand if sustainability forms part of its central policy agenda. As such, the paper focuses on the levels of awareness and disclosure of their sustainable practices, measuring the impacts and effectiveness of those initiatives. This paper introduces signaling theory to explore the idea that appropriate communication via integrated thinking can close the gap between the organization and its stakeholders. We believe that the provision of this relevant information will lead to better communication between the organization and its stakeholders, supporting a signaling theory interpretation. Therefore, we are suggesting that integrated thinking is an internal process that organizations can follow to increase the level of disclosure as a communication tool with stakeholders. From the literature reviewed, four themes were identified (definition of university sustainability, sustainability awareness, disclosure framework within universities, and level of accountability). The research adopted a pragmatic view and conducted individual interviews with participants belonging to three stakeholder groups (members of the university’s senior management, the governing council, and the student union executive). Although this study focused on just one Scottish university, it should still provide some insight for the better understanding of the underpinning issues surrounding the sustainability accountability practices of Scottish universities in general. The research findings indicated that the university prioritized only two sustainability dimensions—economic and environmental—and that the university still perceived sustainability as a voluntary exercise. Additionally, it is evident that the university had no framework in place for measuring its sustainability delivery—and therefore had no established medium of communicating these activities to its stakeholders. Moreover, research findings showed that the social and educational context of sustainability was lacking at the university. The university has done little or nothing to educate its stakeholders on sustainability.


2020 ◽  
Vol 13 (1) ◽  
pp. 279
Author(s):  
Fang Zhao ◽  
Ning Zhu ◽  
Juha Hämäläinen

This study investigated the resilience of the Chinese child protection system in responding to the special needs of children in difficulty under the specific circumstances caused by the COVID-19 pandemic. This study applied qualitative document analysis of child protection administrative documents, in-depth interviews with 13 child protection professionals, and an in-depth case study of 14 children living in difficulty, complemented by relevant information available in the media. The results indicate that there are good policies in China’s child protection services but the organizational and functional fragmentation complicates implementation, suggesting a need for the development of bottom-up practices. The essential conclusion supported by these results is that the child protection system should be regarded and developed as a systematic project combining the legal, policymaking, and professional systems of child welfare services as well as governmental and non-governmental forces. As the COVID-19 pandemic has raised awareness of the need to develop the field of child protection holistically as an integrated system in terms of social sustainability in China, an international literature-based comparison indicates that the pandemic has also raised similar political awareness in other countries.


Author(s):  
Soon Chong Johnson Lim ◽  
Ying Liu ◽  
Wing Bun Lee

In literature, there are a number of indexes suggested that serve as the indicator of commonality among product components, modules and variants. However, as these elements are increasingly interconnected with aspects other than the component view, the existing commonality metrics are unable to effectively model these aspects due to their limitation in capturing relevant information for analysis. Therefore, there exists a need to consider multiple design and manufacturing aspects in commonality metrics so that a comprehensive view of the commonality among product variants can be presented. In the current representation schemes proposed for product family modeling, ontology is one of the most promising ones to model the complex semantic relations among various elements in a product family. Nevertheless, the research and application of ontology in the analysis of a product family has so far received little attention. In this paper, we proposed a framework to generate a semantically annotated multi-facet product family ontology. Using a case study of a laptop computer family, we suggest and demonstrate a new commonality analysis approach based on the semantically annotated multi-facet laptop product family ontology. Together with a new method of deriving product variants based on the aforementioned ontology, our approach illustrates the merits of using semantic annotation in assisting ontology based product family analysis.


2004 ◽  
Vol 06 (02) ◽  
pp. 189-211 ◽  
Author(s):  
MARK LEMON ◽  
PAUL JEFFREY ◽  
BRIAN S. MCINTOSH ◽  
TIM OXLEY

Participation has become part of the language of environmental management. While this move is positive there remains a danger that overly formalised and restricted participatory procedures, in terms of the information sought, may constrain and hinder dialogue and learning between the public and management agencies. Responses to specific issues are often sought from members of the public without a clear understanding about whether those issues are salient to them, where they are salient or how they fit into multiple and dynamic interpretations of environmental change. This paper uses case study material from the UK to demonstrate a novel Pathways Approach to the recording and analysis of individual perceptions about environmental change. The approach seeks to concentrate on experience and interpretation and is based on the conceptualisation of perceived cause–effect relationships and the pathways that support them. The links between time, space and community are considered within this analysis, as is the potential for improved participation through the provision of policy relevant information to planners and environmental managers operating in complex, multi-perspective situations.


Corpora ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. 371-399 ◽  
Author(s):  
Federica Formato

This paper examines the way that the Italian media use language to refer to female ministers in the last three governments. While Italian is a gender-specific language (e.g., a root of the job titles can be followed by either feminine or masculine morphemes, singular and plural), it is common to use masculine forms to refer to and address women. Ministro is one of those cases where masculine forms replace feminine ones – a practice which could be construed as sexist, is only rarely challenged in institutions, and to which attention has only recently been paid in academia ( Fusco, 2012 ; and Robustelli, 2012a , 2012b ). The investigation presented here focusses on how grammar is translated in a way that reproduces women's invisibility in a sexist society. A corpus-based quantitative analysis of feminine and masculine forms of ministr– used in three widely read printed Italian newspapers (Corriere della Sera, Il Resto del Carlino and La Stampa) is undertaken. Newspaper articles were collected in the period 2012–14 to cover the Monti technocratic government (three female ministers), and left-winged Letta (seven female ministers) and part of the Renzi (seven female ministers) political governments. This paper contributes to the literature on language reform and sexist language in traditionally male-inhabited physical and metaphysical (stereotypes, prototypes) spaces such as the institutional public sphere.


2000 ◽  
Vol 74 (9) ◽  
pp. 3948-3952 ◽  
Author(s):  
Christelle Retière ◽  
Virginie Prod'homme ◽  
Berthe-Marie Imbert-Marcille ◽  
Marc Bonneville ◽  
Henri Vié ◽  
...  

ABSTRACT Cytotoxic T lymphocytes (CTLs) play a central role in the control of persistent human cytomegalovirus (HCMV) infection in healthy virus carriers. Previous analyses of the specificity of HCMV-reactive CD8+ CTLs drawn from in vitro models in which antigen-presenting cells were autologous fibroblasts infected with laboratory HCMV strains have shown focusing of CTL responses against the major tegument protein, pp65. By contrast, the 72-kDa major immediate-early protein (IE1) was identified as a minor target for this response. Here we have studied the fine specificity and T-cell-receptor features of T-cell clones generated against autologous B lymphoblastoid cell lines stably transfected with HCMV cDNA coding for either pp65 or a natural variant of IE1. This strategy allowed efficient generation of T-cell clones against IE1 and pp65 and led to the identification of several new IE1 and pp65 epitopes, including some located in polymorphic regions of IE1. Such an approach may provide relevant information about the characteristics of the CTL response to IE1 and the effect of viral polymorphism on the immune response against HCMV.


2021 ◽  
Vol 46 (2) ◽  
pp. 57-63
Author(s):  
Lotte Wilms ◽  
Caleb Derven ◽  
Merisa Martinez

How can European library staff working in digital humanities connect with peers in the library sector, determine where to find relevant information about digital scholarship, provide their collections as data and to be an equal partner in digital humanities research? The LIBER Digital Humanities Working Group was created as a participatory knowledge network in 2017 to address these questions. Through a series of workshops, knowledge sharing activities, and a Europe-wide survey and resulting report, the Working Group engaged with the international LIBER DH community. Useful reflections are provided on organising an open, voluntary DH community and planning for inclusive activities that benefit digital scholarship in European research libraries.


Author(s):  
Ekaterina Savitskaya ◽  

In the field of cognitive linguistics it is accepted that, before developing its capacity for abstract and theoretical thought, the human mind went through the stage of reflecting reality through concrete images and thus has inherited old cognitive patterns. Even abstract notions of the modern civilization are based on traditional concrete images, and it is all fixed in natural language units. By way of illustration, the author analyzes the cognitive pattern “сleanness / dirtiness” as a constituent part of the English linguoculture, looking at the whole range of its verbal realization and demonstrating its influence on language-based thinking and modeling of reality. Comparing meanings of language units with their inner forms enabled the author to establish the connection between abstract notions and concrete images within cognitive patterns. Using the method of internal comparison and applying the results of etymological reconstruction of language units’ inner form made it possible to see how the world is viewed by representatives of the English linguoculture. Apparently, in the English linguoculture images of cleanness / dirtiness symbolize mainly two thematic areas: that of morality and that of renewal. Since every ethnic group has its own axiological dominants (key values) that determine the expressiveness of verbal invectives, one can draw the conclusion that people perceive and comprehend world fragments through the prism of mental stereo-types fixed in the inner form of language units. Sometimes, in relation to specific language units, a conflict arises between the inner form which retains traditional thinking and a meaning that reflects modern reality. Still, linguoculture is a constantly evolving entity, and its de-velopment entails breaking established stereotypes and creating new ones. Linguistically, the victory of the new over the old is manifested in the “dying out” of the verbal support for pre-vious cognitive patterns, which leads to “reprogramming” (“recoding”) of linguoculture rep-resentatives’ mentality.


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