A Macro-scale Comparison Algorithm for Analysis of TCR Repertoire Completeness

AbstractRecent advances in biotechnology are beginning to generate whole immunome datasets, which will enable the comparison of immune repertoires between individuals, e.g., to assess immunocompetence. Existing algorithms cluster cell types based on the relative expression abundance of about 20 000 genes, but such algorithms have limited utility when comparing immunome datasets with many higher orders of magnitude (>1012) of variation, such as occurs in immunoreceptor sequences in highly polyclonal naive repertoires.In this paper we present a method for comparing immune repertoires by identifying macro-level features that are conserved between similar individuals. Our method allows us to detect some blind spots in naive populations and to assess whether a repertoire is likely complete by examining only a sample of its sequences.Author SummaryIn this paper we present a method for comparing the immune repertoire of different individuals. Repertoires are represented by a sample of genetic sequences. Our technique coarse grains each individual’s data into groups, matches groups between individual’s and finds significant differences.

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Underground waterlines

Focaal ◽

10.3167/fcl.2019.032103 ◽

2019 ◽

pp. 1-14

Author(s):

Denys Gorbach

Keyword(s):

Macro Level ◽

The Political ◽

Macro Scale ◽

Ethnographic Data ◽

Economic Boom ◽

Labor Hoarding ◽

Large Enterprises

In order to explore factors conditioning the political quietude of Ukrainian labor, this article analyzes ethnographic data collected at two large enterprises: the Kyiv Metro and the privatized electricity supplier Kyivenergo. Focusing on a recent labor conflict, I unpack various contexts condensed in it. I analyze the hegemonic configuration developed in the early 1990s, at the workplace and at the macro level, and follow its later erosion. This configuration has been based on labor hoarding, distribution of nonwage resources, and patronage networks, featuring the foreman as the nodal figure. On the macro scale, it relied on the mediation by unions, supported by resources accumulated during the Soviet era and the economic boom of the 2000s. The depletion of these resources has spelled the ongoing crisis of this configuration.

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Homogenization of trabecular structures

MATEC Web of Conferences ◽

10.1051/matecconf/202031000041 ◽

2020 ◽

Vol 310 ◽

pp. 00041

Author(s):

Tomáš Krejčí ◽

Aleš Jíra ◽

Luboš Řehounek ◽

Michal Šejnoha ◽

Jaroslav Kruis ◽

...

Keyword(s):

Finite Element ◽

Effective Properties ◽

Macro Level ◽

Truss Structures ◽

Scale Analysis ◽

Scale Problem ◽

Meso Level ◽

Multi Scale ◽

Macro Scale ◽

Multi Scale Analysis

Numerical modeling of implants and specimens made from trabecular structures can be difficult and time-consuming. Trabecular structures are characterized as spatial truss structures composed of beams. A detailed discretization using the finite element method usually leads to a large number of degrees of freedom. It is attributed to the effort of creating a very fine mesh to capture the geometry of beams of the structure as accurately as possible. This contribution presents a numerical homogenization as one of the possible methods of trabecular structures modeling. The proposed approach is based on a multi-scale analysis, where the whole specimen is assumed to be homogeneous at a macro-level with assigned effective properties derived from an independent homogenization problem at a meso-level. Therein, the trabecular structure is seen as a porous or two-component medium with the metal structure and voids filled with the air or bone tissue at the meso-level. This corresponds to a two-level finite element homogenization scheme. The specimen is discretized by a reasonable coarse mesh at the macro-level, called the macro-scale problem, while the actual microstructure represented by a periodic unit cell is discretized with sufficient accuracy, called the meso-scale problem. Such a procedure was already applied to modeling of composite materials or masonry structures. The application of this multi-scale analysis is illustrated by a numerical simulation of laboratory compression tests of trabecular specimens.

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Development of a Micro-Scale Differential Scanning Calorimeter for Single Cell Measurements

ASME/JSME 2007 Thermal Engineering Heat Transfer Summer Conference, Volume 3 ◽

10.1115/ht2007-32555 ◽

2007 ◽

Author(s):

William G. Zhao ◽

Gary L. Solbrekken ◽

Steven F. Mullen ◽

James D. Benson ◽

Xu Han ◽

...

Keyword(s):

Phase Change ◽

Single Cell ◽

Extended Period ◽

Cell Types ◽

Biological Materials ◽

Micro Scale ◽

Heating And Cooling ◽

Macro Scale ◽

In Series ◽

Change Temperature

Cryopreservation is an effective way to store biological materials for an extended period of time. The process of freezing biological materials is rather traumatic, however, due to the water phase change that takes place. Successful cooling procedures have been developed for a limited number of cell types primarily through a large amount of experimentation. Fundamental cryobiological studies of cellular heat and mass transfer are currently under way in an attempt to develop an accurate model that will reduce the need for many costly experiments. The purpose of this paper is to describe the development of a tool that will allow more accurate measurements of the phase change temperature for a single cell (∼100 μm diameter) as it freezes. The resulting data will be used to improve the fundamental cryopreservation model. A proof-of-concept micro-scale DSC (μDSC) is designed and built using 250 μm × 250 μm × 500 μm thermoelectric elements. The elements are connected electrically in series to one another with metal electrodes that double as the sample and reference pans. The advantage of this configuration is that Peltier heating and cooling of the sample each have the same time constant, in contrast with macro-scale DSC machines. Thermocouples with 25 μm beads are attached to the pans providing the local temperature of the sample used for feedback control. The feedback temperature is used as the control signal for the power supply which supplies electric current to the thermoelectric structure described above. Initial experiments on the prototype μDSC indicate that the phase change of a single swine oocyte with a diameter of about 100 μm can be detected.

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Underground waterlines

Focaal ◽

10.3167/fcl.2019.840103 ◽

2019 ◽

Vol 2019 (84) ◽

pp. 33-46 ◽

Cited By ~ 2

Author(s):

Denys Gorbach

Keyword(s):

Macro Level ◽

The Political ◽

Macro Scale ◽

Ethnographic Data ◽

Economic Boom ◽

Labor Hoarding ◽

Large Enterprises

In order to explore factors conditioning the political quietude of Ukrainian labor, this article analyzes ethnographic data collected at two large enterprises: the Kyiv Metro and the privatized electricity supplier Kyivenergo. Focusing on a recent labor conflict, I unpack various contexts condensed in it. I analyze the hegemonic configuration developed in the early 1990s, at the workplace and at the macro level, and follow its later erosion. Th is configuration has been based on labor hoarding, distribution of nonwage resources, and patronage networks, featuring the foreman as the nodal figure. On the macro scale, it relied on the mediation by unions, supported by resources accumulated during the Soviet era and the economic boom of the 2000s. The depletion of these resources has spelled the ongoing crisis of this configuration.

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TCRdb: a comprehensive database for T-cell receptor sequences with powerful search function

Nucleic Acids Research ◽

10.1093/nar/gkaa796 ◽

2020 ◽

Vol 49 (D1) ◽

pp. D468-D474 ◽

Cited By ~ 1

Author(s):

Si-Yi Chen ◽

Tao Yue ◽

Qian Lei ◽

An-Yuan Guo

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Length Distribution ◽

Cell Types ◽

Cell Receptor ◽

Search Function ◽

Tcr Repertoire ◽

Tcr Diversity ◽

Clinical Conditions ◽

T Cell Immunology

Abstract T cells and the T-cell receptor (TCR) repertoire play pivotal roles in immune response and immunotherapy. TCR sequencing (TCR-Seq) technology has enabled accurate profiling TCR repertoire and currently a large number of TCR-Seq data are available in public. Based on the urgent need to effectively re-use these data, we developed TCRdb, a comprehensive human TCR sequences database, by a uniform pipeline to characterize TCR sequences on TCR-Seq data. TCRdb contains more than 277 million highly reliable TCR sequences from over 8265 TCR-Seq samples across hundreds of tissues/clinical conditions/cell types. The unique features of TCRdb include: (i) comprehensive and reliable sequences for TCR repertoire in different samples generated by a strict and uniform pipeline of TCRdb; (ii) powerful search function, allowing users to identify their interested TCR sequences in different conditions; (iii) categorized sample metadata, enabling comparison of TCRs in different sample types; (iv) interactive data visualization charts, describing the TCR repertoire in TCR diversity, length distribution and V-J gene utilization. The TCRdb database is freely available at http://bioinfo.life.hust.edu.cn/TCRdb/ and will be a useful resource in the research and application community of T cell immunology.

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Like Follicle, like Fibre? Diameter and not Follicle Type Correlates with Fibre Ultrastructure

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.671.88 ◽

2015 ◽

Vol 671 ◽

pp. 88-94 ◽

Cited By ~ 3

Author(s):

Duane Harland ◽

Joy Woods ◽

James Vernon ◽

Richard Walls ◽

David Scobie ◽

...

Keyword(s):

Electron Microscopy ◽

Fibre Diameter ◽

Cell Types ◽

Hair Follicles ◽

Sheep Breeds ◽

Cortex Cell ◽

Macro Scale ◽

Significant Difference ◽

Structural Differences ◽

Fibre Parameter

The hair follicles of most mammals are of two types, primary and secondary. Primary follicles develop earlier and have a prominent arrectorpili muscle. Secondary follicles have less prominent muscles and are often clumped, sharing a common opening from which fibres emerge. It is not entirely clear what types of follicles occur in human scalps. Partly this is because human hairs have a uniform appearance, unlike many mammals in which robust primary hairs differ markedly from narrow secondary fibres. Some sheep breeds are an exception because like humans, wool fibres have a similar macro-scale appearance irrespective of follicle type. How deep does this similarity go? Using electron microscopy, we examined wool primary fibres from different breeds and contrasted them to secondary fibres. For fibres of similar diameter, there was no significant difference in the ultrastructure or proportion and distribution of cortex cell types in primary and secondary fibres. We conclude that fibre diameter is the most important fibre parameter with respect to structural differences between fibres, not whether the fibres originate from primary or secondary follicles.

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Resident memory CD8 T cells persist for years in human small intestine

10.1101/553792 ◽

2019 ◽

Cited By ~ 2

Author(s):

Raquel Bartolomé Casado ◽

Ole J.B. Landsverk ◽

Sudhir Kumar Chauhan ◽

Lisa Richter ◽

Dang Phung ◽

...

Keyword(s):

T Cells ◽

Small Intestine ◽

Lamina Propria ◽

Cd8 T Cells ◽

List Type ◽

Immune Repertoire ◽

Memory Cd8 T Cells ◽

Human Small Intestine ◽

Tcr Repertoire ◽

One Year

In human small intestine, most CD8 T cells in the lamina propria and epithelium express a resident memory (Trm) phenotype and persist for at least one year in transplanted tissue. Intestinal CD8 Trm cells have a clonally expanded immune repertoire that is stable over time and exhibit enhanced protective capabilities.Graphical abstractHighlightsThe vast majority of CD8 T cells in the human small intestine are Trm cellsCD8 Trm cells persist for >1 year in transplanted duodenumIntraepithelial and lamina propria CD8 Trm cells show highly similar TCR repertoireIntestinal CD8 Trm cells efficiently produce cytokines and cytotoxic mediators

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The ORF8 Protein of SARS-CoV-2 Mediates Immune Evasion through Potently Downregulating MHC-I

10.1101/2020.05.24.111823 ◽

2020 ◽

Cited By ~ 38

Author(s):

Yiwen Zhang ◽

Junsong Zhang ◽

Yingshi Chen ◽

Baohong Luo ◽

Yaochang Yuan ◽

...

Keyword(s):

Immune Surveillance ◽

Cell Types ◽

Surface Expression ◽

Viral Immunity ◽

Mhc I ◽

Reading Frame ◽

Global Pandemic ◽

Infected Cells ◽

Genetic Sequences

SummarySARS-CoV-2 infection have caused global pandemic and claimed over 5,000,000 tolls1–4. Although the genetic sequences of their etiologic viruses are of high homology, the clinical and pathological characteristics of COVID-19 significantly differ from SARS5,6. Especially, it seems that SARS-CoV-2 undergoes vast replication in vivo without being effectively monitored by anti-viral immunity7. Here, we show that the viral protein encoded from open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all the viral proteins, can directly interact with MHC-I molecules and significantly down-regulates their surface expression on various cell types. In contrast, ORF8a and ORF8b of SARS-CoV do not exert this function. In the ORF8-expressing cells, MHC-I molecules are selectively target for lysosomal degradation by an autophagy-dependent mechanism. As a result, CTLs inefficiently eliminate the ORF8-expressing cells. Our results demonstrate that ORF8 protein disrupts antigen presentation and reduces the recognition and the elimination of virus-infected cells by CTLs8. Therefore, we suggest that the inhibition of ORF8 function could be a strategy to improve the special immune surveillance and accelerate the eradication of SARS-CoV-2 in vivo.

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Macro-scale phenomena of arterial coupled cells: a massively parallel simulation

Journal of The Royal Society Interface ◽

10.1098/rsif.2011.0453 ◽

2011 ◽

Vol 9 (70) ◽

pp. 972-987 ◽

Cited By ~ 7

Author(s):

Mohsin Ahmed Shaikh ◽

David J. N. Wall ◽

Tim David

Keyword(s):

Cell Types ◽

Inhibitory Effect ◽

Massively Parallel ◽

Arterial Segment ◽

Micro Scale ◽

Spatial Gradients ◽

Macro Scale ◽

Large Populations ◽

Intracellular Ca ◽

Blue Gene

Impaired mass transfer characteristics of blood-borne vasoactive species such as adenosine triphosphate in regions such as an arterial bifurcation have been hypothesized as a prospective mechanism in the aetiology of atherosclerotic lesions. Arterial endothelial cells (ECs) and smooth muscle cells (SMCs) respond differentially to altered local haemodynamics and produce coordinated macro-scale responses via intercellular communication. Using a computationally designed arterial segment comprising large populations of mathematically modelled coupled ECs and SMCs, we investigate their response to spatial gradients of blood-borne agonist concentrations and the effect of micro-scale-driven perturbation on the macro-scale. Altering homocellular (between same cell type) and heterocellular (between different cell types) intercellular coupling, we simulated four cases of normal and pathological arterial segments experiencing an identical gradient in the concentration of the agonist. Results show that the heterocellular calcium (Ca 2+ ) coupling between ECs and SMCs is important in eliciting a rapid response when the vessel segment is stimulated by the agonist gradient. In the absence of heterocellular coupling, homocellular Ca 2+ coupling between SMCs is necessary for propagation of Ca 2+ waves from downstream to upstream cells axially. Desynchronized intracellular Ca 2+ oscillations in coupled SMCs are mandatory for this propagation. Upon decoupling the heterocellular membrane potential, the arterial segment looses the inhibitory effect of ECs on the Ca 2+ dynamics of the underlying SMCs. The full system comprises hundreds of thousands of coupled nonlinear ordinary differential equations simulated on the massively parallel Blue Gene architecture. The use of massively parallel computational architectures shows the capability of this approach to address macro-scale phenomena driven by elementary micro-scale components of the system.

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Proper Read Filtering Method to Adequately Analyze Whole-Transcriptome Sequencing and RNA Based Immune Repertoire Sequencing Data for Tumor Milieu Research

Cancers ◽

10.3390/cancers12123693 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3693

Author(s):

Sungyoung Lee ◽

Seulki Song ◽

Sung-Soo Yoon ◽

Youngil Koh ◽

Hongseok Yun

Keyword(s):

T Cell ◽

Transcriptome Sequencing ◽

High Throughput Sequencing ◽

Capture Rate ◽

Immune Repertoire ◽

Filtering Method ◽

Tcr Repertoire ◽

Whole Transcriptome Sequencing ◽

Repertoire Sequencing ◽

Whole Transcriptome

Analysis of the T-cell receptor (TCR) repertoire is essential to characterize the extensive collections of T-cell populations with recognizing antigens in cancer research, and whole transcriptome sequencing (WTS) and immune repertoire sequencing (IR-seq) are commonly used for this measure. To date, no standard read filtering method for IR measurement has been presented. We assessed the diversity of the TCR repertoire results from the paired WTS and IR-seq data of 31 multiple myeloma (MM) patients. To invent an adequate read filtering strategy for IR analysis, we conducted comparisons with WTS results. First, our analyses for determining an optimal threshold for selecting clonotypes showed that the clonotypes supported by a single read largely affected the shared clonotypes and manifested distinct patterns of mapping qualities, unlike clonotypes with multiple reads. Second, although IR-seq could reflect a wider TCR region with a higher capture rate than WTS, an adequate comparison with the removal of unwanted bias from potential sequencing errors was possible only after applying our read filtering strategy. As a result, we suggest that TCR repertoire analysis be carried out through IR-seq to produce reliable and accurate results, along with the removal of single-read clonotypes, to conduct immune research in cancer using high-throughput sequencing.

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