In silico analysis revealed Zika virus miRNAs associated with viral pathogenesis through alteration of host genes involved in immune response and neurological functions

2019 ◽  
Vol 91 (9) ◽  
pp. 1584-1594 ◽  
Author(s):  
Md. Sajedul Islam ◽  
Md. Abdullah‐Al‐Kamran Khan ◽  
Md. Wahid Murad ◽  
Marwah Karim ◽  
Abul Bashar Mir Md. Khademul Islam
Keyword(s):  
Immune Response ◽  
Zika Virus ◽  
In Silico ◽  
In Silico Analysis ◽  
Viral Pathogenesis ◽  
Silico Analysis ◽  
Host Genes

scholarly journals 325 Eliminating tumor immune privilege through immune checkpoint cytoreduction

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A350-A350
Author(s):  
Michelle Winkler ◽  
Michael Curran
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Tumor Cells ◽  
In Silico ◽  
In Silico Analysis ◽  
Immune Privilege ◽  
Cell Populations ◽  
List Type ◽  
Immune Effector ◽  
Silico Analysis

BackgroundAnti-checkpoint antibodies blocking T cell co-inhibitory molecules (e.g. αPD-1, αCTLA-4) allow immune effector cells to persist, expand, and maintain cytotoxic function in the tumor microenvironment (TME). Despite being effective in immune ”hot” tumors that are infiltrated by effector anti-tumor cells, immune ”cold” tumors fail to respond to checkpoint blockade. ”Cold” tumors are populated with immune suppressive cells including regulatory T cells, M2 macrophages, and myeloid derived suppressor cells, which inhibit immune effector infiltration and function. These suppressive populations, along with tumor cells, express co-inhibitory checkpoints already targeted with current immunotherapeutics, but also some checkpoints in need of further investigation. We hypothesized that by targeting these checkpoints with cytoreductive antibodies which selectively deplete suppressive populations and tumor cells via ADCC/ADCP, we will compromise ”cold” immune privilege and restore an efficient anti-tumor immune response.MethodsTo identify novel targets to produce checkpoint cytoreductive antibodies we conducted in silico analysis that prioritized immune-inhibitory targets with tumor-specific or tumor-selective expression on cell surface. We cross-referenced a previously published list of transmembrane proteins against publicly sourced datasets including TCGA, HPA, GTEx, BioGPS, and SAGE.1 We then characterized the expression profile of each selected target on tumor cells in vitro and on cell populations in the TME ex vivo via multiparameter flow cytometry. Finally, we assessed the impact of existing checkpoint-targeting cytoreductive antibodies on survival and tumor growth in murine ”hot” and ”cold” tumors.ResultsVISTA and DLL3 were identified via in silico analysis as co-inhibitory surface proteins specifically and selectively in the TME and not in healthy tissues. DLL3 is mainly expressed on tumor cells while VISTA was described mostly on immunosuppressive myeloid cells. An anti-DLL3 antibody was produced by a previous laboratory as an IgG1 antibody, and we engineered a version in the depletive (IgG2a) isotype, which will enable us to target this checkpoint with either a blocking or a depleting antibody. Flow cytometry analysis identified VISTA on multiple myeloid cell populations in ”cold” 4T1 murine mammary tumors while its expression was low in spleen. To start assessing the efficiency of depleting versus non-depleting antibodies, ”hot” CT26 murine tumors and 4T1 tumors were treated with an αCTLA-4-IgG2a or αCTLA-4-IgG1. Groups treated with depleting antibodies showed increased survival compared to groups treated with non-depleting antibodies.ConclusionsNovel immune-inhibitory checkpoints can be identified and targeting them with cytoreductive antibodies leads to a higher anti-tumor immune response. This investigation opens the door to more efficient combination therapies.AcknowledgementsSupported by a training fellowship from The University of Texas Health Science Center at Houston Center for Clinical and Translational Sciences TL1 Program (Grant No. TL1 TR003169).ReferencesWang J, et al. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nat Med 25,(2019).

scholarly journals In-Depth In Silico Search for Cuttlefish (Sepia officinalis) Antimicrobial Peptides Following Bacterial Challenge of Haemocytes

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 439
Author(s):  
Louis Benoist ◽  
Baptiste Houyvet ◽  
Joël Henry ◽  
Erwan Corre ◽  
Bruno Zanuttini ◽  
...  
Keyword(s):  
Immune Response ◽  
Antimicrobial Peptides ◽  
In Silico ◽  
De Novo ◽  
In Silico Analysis ◽  
Sepia Officinalis ◽  
Vibrio Splendidus ◽  
Pattern Searches ◽  
Sequence Characteristics ◽  
Silico Analysis

Cuttlefish (Sepia officinalis) haemocytes are potential sources of antimicrobial peptides (AMPs). To study the immune response to Vibrio splendidus and identify new AMPs, an original approach was developed based on a differential transcriptomic study and an in-depth in silico analysis using multiple tools. Two de novo transcriptomes were retrieved from cuttlefish haemocytes following challenge by V. splendidus or not. A first analysis of the annotated transcripts revealed the presence of Toll/NF-κB pathway members, including newly identified factors such as So-TLR-h, So-IKK-h and So-Rel/NF-κB-h. Out of the eight Toll/NF-κB pathway members, seven were found up-regulated following V. splendidus challenge. Besides, immune factors involved in the immune response were also identified and up-regulated. However, no AMP was identified based on annotation or conserved pattern searches. We therefore performed an in-depth in silico analysis of unannotated transcripts based on differential expression and sequence characteristics, using several tools available like PepTraq, a homemade software program. Finally, five AMP candidates were synthesized. Among them, NF19, AV19 and GK28 displayed antibacterial activity against Gram-negative bacteria. Each peptide had a different spectrum of activity, notably against Vibrio species. GK28—the most active peptide—was not haemolytic, whereas NF19 and AV19 were haemolytic at concentrations between 50 and 100 µM, 5 to 10 times higher than their minimum inhibitory concentration.

scholarly journals In Silico Analysis of the Longevity and Timeline of Individual Germinal Center Reactions in a Primary Immune Response

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1736
Author(s):  
Theinmozhi Arulraj ◽  
Sebastian C. Binder ◽  
Michael Meyer-Hermann
Keyword(s):  
Immune Response ◽  
In Silico ◽  
Late Phase ◽  
Critical Factor ◽  
In Silico Analysis ◽  
Lymphoid Organ ◽  
Affinity Maturation ◽  
Primary Immune Response ◽  
Average Lifetime ◽  
Silico Analysis

Germinal centers (GCs) are transient structures in the secondary lymphoid organs, where B cells undergo affinity maturation to produce high affinity memory and plasma cells. The lifetime of GC responses is a critical factor limiting the extent of affinity maturation and efficiency of antibody responses. While the average lifetime of overall GC reactions in a lymphoid organ is determined experimentally, the lifetime of individual GCs has not been monitored due to technical difficulties in longitudinal analysis. In silico analysis of the contraction phase of GC responses towards primary immunization with sheep red blood cells suggested that if individual GCs had similar lifetimes, the data would be consistent only when new GCs were formed until a very late phase after immunization. Alternatively, there could be a large variation in the lifetime of individual GCs suggesting that both long and short-lived GCs might exist in the same lymphoid organ. Simulations predicted that such differences in the lifetime of GCs could arise due to variations in antigen availability and founder cell composition. These findings identify the potential factors limiting GC lifetime and contribute to an understanding of overall GC responses from the perspective of individual GCs in a primary immune response.

In silico analysis of anti-leukemia immune response and immune evasion in acute myeloid leukemia

2018 ◽  
Vol 59 (10) ◽  
pp. 2493-2496
Author(s):  
Rosemarie Krupar ◽  
Cleopatra Schreiber ◽  
Anne Offermann ◽  
Claudia Lengerke ◽  
Andrew G. Sikora ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Myeloid Leukemia ◽  
Immune Evasion ◽  
In Silico ◽  
Myeloid Leukemia ◽  
In Silico Analysis ◽  
Silico Analysis ◽  
Acute Myeloid

scholarly journals In Silico Analysis of Possible Interaction between Host Genomic Transcription Factors and Zika Virus (ZikaSPH2015) Strain with Combinatorial Gene Regulation; Virus Versus Host - The Game Reloaded

2020 ◽  
Author(s):  
Massimiliano Chetta ◽  
Marina Tarsitano ◽  
Laura Vicari ◽  
Annalisa Saracino ◽  
Nenad Bukvic
Keyword(s):  
Transcription Factors ◽  
Zika Virus ◽  
In Silico ◽  
Genomic Sequence ◽  
In Silico Analysis ◽  
Entire Genome ◽  
Severe Condition ◽  
Binding Motifs ◽  
Virus Versus ◽  
Silico Analysis

In silico analysis is a promising approach for understanding biological events in complex diseases. Herein, we report an in silico analysis of the entire genome of virus ZikaSPH2015 strain, which was performed in order to identify the occurrence of specific motifs on genomic sequence of Zika Virus that is able to bind and therefore, sequester host’s Transcription Factors (TFs) as well as subsequently predict a possible interactions within host genome. Accordingly to obtained results of this original computational work-flow it is possible to hypothesize that these TFs Binding Motifs might be able to explain the complex and heterogeneous phenotype presentation in Zika Virus affected fe-tus/newborns, as well as the less severe condition in adults. Moreover, the proposed in silico protocol identified thirty three different TFs same as the distribution of TFBSs (Transcription Factor Binding Sites) on ZikaSPH2015 strain, potentially able to influence genes and pathways with biological functions confirming that this approach could find potential answers on disease pathogenesis.

scholarly journals In silico analysis reveals EP300 as a panCancer inhibitor of anti-tumor immune response via metabolic modulation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rosemarie Krupar ◽  
Christian Watermann ◽  
Christian Idel ◽  
Julika Ribbat-Idel ◽  
Anne Offermann ◽  
...  
Keyword(s):  
Immune Response ◽  
In Silico ◽  
In Silico Analysis ◽  
Metabolic Modulation ◽  
Silico Analysis

scholarly journals In Silico Analysis of Possible Interaction between Host Genomic Transcription Factors (TFs) and Zika Virus (ZikaSPH2015) Strain with Combinatorial Gene Regulation; Virus Versus Host—The Game Reloaded

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 69
Author(s):  
Massimiliano Chetta ◽  
Marina Tarsitano ◽  
Laura Vicari ◽  
Annalisa Saracino ◽  
Nenad Bukvic
Keyword(s):  
Transcription Factors ◽  
Zika Virus ◽  
In Silico ◽  
In Silico Analysis ◽  
Entire Genome ◽  
Severe Condition ◽  
Binding Motifs ◽  
Virus Sequence ◽  
Virus Versus ◽  
Silico Analysis

In silico analysis is a promising approach for understanding biological events in complex diseases. Herein we report on the innovative computational workflow allowed to highlight new direct interactions between human transcription factors (TFs) and an entire genome of virus ZikaSPH2015 strain in order to identify the occurrence of specific motifs on a genomic Zika Virus sequence that is able to bind and, therefore, sequester host’s TFs. The analysis pipeline was performed using different bioinformatics tools available online (free of charge). According to obtained results of this in silico analysis, it is possible to hypothesize that these TFs binding motifs might be able to explain the complex and heterogeneous phenotype presentation in Zika-virus-affected fetuses/newborns, as well as the less severe condition in adults. Moreover, the proposed in silico protocol identified thirty-three different TFs identical to the distribution of TFBSs (Transcription Factor Binding Sites) on ZikaSPH2015 strain, potentially able to influence genes and pathways with biological functions confirming that this approach could find potential answers on disease pathogenesis.

A systematic review with in silico analysis on transcriptomic profile of gallbladder carcinoma

2020 ◽  
Vol 47 (6) ◽  
pp. 398-408
Author(s):  
Sonam Tulsyan ◽  
Showket Hussain ◽  
Balraj Mittal ◽  
Sundeep Singh Saluja ◽  
Pranay Tanwar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Gallbladder Carcinoma ◽  
In Silico ◽  
In Silico Analysis ◽  
Transcriptomic Profile ◽  
Silico Analysis
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