Biology subjects

Efroni, S.

Publications and source records attributed to Efroni, S..

4 recordsLinked to original sources

bioRxiv2020

CDR3 and V- genes show distinct reconstitution patterns in T-cell repertoire post allogenic bone marrow transplantation

BackgroundRestoration of T-cell repertoire diversity after allogeneic bone marrow transplantation (allo-BMT) is crucial for immune recovery. T-cell diversity is produced by rearrangements of germline gene segments (V (D) and J) of the T-cell receptor (TCR) and {beta} chains, and selection induced by binding of TCRs to MHC-peptide complexes. This diversity can be measured by many measures. We here focus on the V gene usage and the CDR3 sequences of the beta chain. We compared multiple T-cell repertoires to follow T cell repertoire changes post allo-BMT in HLA-matched related donor and recipient pairs. ResultsOur analyses of the differences between donor and recipient complementarity determining region 3 (CDR3) beta composition and V-gene profile show that the CDR sequence composition does not change during restoration, implying its dependence on the HLA typing. In contrast, V gene usage followed a time-dependent pattern, got following the donor profile post transplant and then shifting back to the recipients profile. The final long-term repertoire was more similar to that of the recipients original one than the donors.; some recipients converged within months while others took multiple years. ConclusionBased on the results of our analyses, we propose that donor-recipient V-gene distribution differences may serve as clinical biomarkers for monitoring immune recovery.

immunology↗

bioRxiv2019

A modeling algorithm for exploring the architecture and construction of bird nests

Natural biological structures are often complex and cannot be mapped directly to genes, being therefore impossible to explore by traditional biological tools. In contrast, digitizing these structures enables to explore their properties and behavior under specific conditions, by means of computational manipulations, simulations, and analyses. We describe a generic algorithm for the digitization and exploration of the complex structures exhibited by common, interwoven bird nests. This algorithm takes as input computerized tomographic scans of the studied Dead-Sea Sparrow (Passer moabiticus) nest, identifies and isolates each branch entity within the three-dimensional data and finally extracts the characteristics of each branch. The result is a reliable three-dimensional numerical model of the nest that contains a complete geometric dataset per each of its components, e.g. dimensions and contact points with neighboring components, as well as global properties, e.g. density distribution and network structure. Based on these, we were able to simulate various models of the nest construction process. Altogether, the described algorithm and possible derivatives thereof could be a valuable tool in studying the structure-function relationships of similarly complex biological objects.

biophysics↗

bioRxiv2018

Digital therapeutics for distributed response to global pandemics

Despite advances in the development of drugs and vaccines, the spread of infectious diseases remains an imminent threat to our global health, in extreme cases potentially having detrimental consequences. At present our response to this threat is based on physically distributing therapeutic material, which utilizes the same transportation networks that support the spread of the infectious agent itself. Such competition is at risk of failure in the face of a rapidly spreading pathogen, especially given the inevitable delay from the initial outbreak to the development and execution of our response. Moreover, based on our existing transportation networks, we show that such physical distribution is intrinsically inefficient, leading to an uneven concentration of the therapeutic within a small fraction of destinations, while leaving the majority of the population deprived. This suggests that outrunning a virulent epidemic can only be achieved if we develop a mitigation strategy that bypasses the existing distribution networks of biological and chemical material. Here we propose such a response, utilizing digitizable therapeutics, which can be distributed as digital sequence files and synthesized on location, exposing an extremely efficient mitigation scheme that systematically outperforms physical distribution. Our proposed strategy, based for example on nucleic acid therapeutics, is plausibly the only viable mitigation plan, based on current technology, that can face a violently spreading pathogen. Complementing the current paradigm, which ranks drugs based on efficacy, our analysis demonstrates the importance of balancing efficacy with distributability, finding that in some cases the latter plays the dominant role in the overall mitigation efficiency.

bioinformatics↗

bioRxiv2018

Mice developing mammary tumors evolve T cell sequences shared with human breast cancer patients

Cancer immunotherapy by checkpoint blockade proves that an effective immune response to a tumor can be induced clinically. However, little is known about the evolution of tumor-associated T-cell receptor (TCR) repertoires without intervention. Here we studied TCR repertoire evolution in mice spontaneously developing mammary tumors; we sequenced peripheral blood alpha and beta TCRs of CD4+CD62L+CD44- T cells monthly for 8 months in 10 FVB/NJ mice transgenic at the Erbb2 locus, all developing tumors; 5 FVB/NJ mice without the transgene were age-matched controls. Sequences were either private (restricted to one mouse) or public (shared among mice); public sequences were either exclusive to the tumor group or inclusive among different groups. We now report that 1), public AA sequences were each encoded by many different nucleotide sequences (NT) recombinations (convergent recombination; CR); 2) mice developing tumors evolved tumor-exclusive public sequences, derived initially from private or from inclusive public sequences; and 3) tumor-exclusive public sequences in mice were also present among published public TCR sequences from human breast cancer patients. These cross-species tumor-exclusive TCR sequences manifested high CR; but the AA sequences shared by mice and humans did not share NT sequences. Thus, tumor-exclusive TCR AA sequences across species are selected from different NT recombination events. The roles of tumor-exclusive TCR repertoires in advancing or inhibiting tumor development and the effects of tumor immunotherapy on these T cells remain to be seen.

cancer biology↗