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Streptococcus pneumoniae and Influenza (H1N1) virus Genome Study Against Human Genome Sequences – Blastn and DAVID Analysis

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31 July 2023

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02 August 2023

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Abstract
Aim: Streptococcus pneumoniae and influenza H1N1 virus are common organisms associated with human infections. These infections could play a significant role in immune regulation. The study was performed to analyse the genome sequences of these organisms with human genome and study its functional significance. Methods: The study was performed to analyse the overlapping of genome sequences in Streptococcus pneumoniae and Influenza (H1N1) virus against human genome sequences by BLASTn sequence analysis. The alignments are studied against the corresponding genes for their functional significance with DAVID and NDEx software.Results: Several hits or overlapping nucleotide segments were identified. Between streptococcus and homo sapiens 287 overlaps were identified, and among influenza and homo sapiens 124 hits were identified. A wide range of functional significance of these genes were identified, and the results are presented in this study. The results show insights into functional pathways and biological activities associated with the respective vaccinations or infections by these microorganisms. Conclusion: The common organisms like Streptococcus pneumoniae and Influenza H1N1 virus actively interact with the immune system and result in a wide range of immune regulations.
Keywords: 
Subject: Medicine and Pharmacology  -   Immunology and Allergy

Introduction

Streptococcus pneumoniae and influenza (H1N1) are common vaccinations given to the elderly general population. Infections by these organisms are associated with mortality and morbidity worldwide, and the regional incidence varies [1]. Vaccinations against these organisms are associated with cardiovascular benefits and also a general reduction in mortality [2,3,4]. Improvement in trained immunity has been postulated for non-specific protection of these vaccinations against Covid19 [5]. The exact mechanisms of this protection. The study was performed to analyze the genome sequence overlap between these microorganisms and the human genome and to evaluate the possible modifications and influences of these vaccinations on human gene expression.

Methods

Blastn analysis [6,7] was performed by comparing the Streptococcus pneumoniae strain Hu17 and Haemophilus influenza (H1N1) 2009 California genome sequences against the human genome (Homo sapiens Hg38). The genome sequence of Influenza H1N1 2009 California (2009 California) was downloaded from NCBI (https://www.ncbi.nlm.nih.gov/data-hub/taxonomy/641809/). The Influenza H1N1 2009 California genome sequences were compared against Homo sapiens hg38 downloaded from NCBI (https://www.ncbi.nlm.nih.gov/assembly/GCF_000001405.26/) with blastn tools (2.13.0+) on a Linux server, respectively. The genome sequence of Streptococcus Pneumonia strain Hu17 (2009 California) was downloaded from NCBI (https://www.ncbi.nlm.nih.gov/data-hub/taxonomy/641809/). The Streptococcus pneumoniae strain Hu17 genome sequences were compared against Homo sapiens hg38 downloaded from NCBI (https://www.ncbi.nlm.nih.gov/assembly/GCF_00000 1405.26/) with blastn tools (2.13.0+) on a Linux server, respectively. The hits/alignments on the genome of Homo sapiens hg38 reported by the blast analysis were retrieved with customized Python scripts. The regions of hits were annotated with gene information, respectively.
The corresponding genes were studied for functional annotations to study background processes, which could influence physiological changes. The blast analysis results were further processed for functional analysis of the concerned genes through the database for annotation, visualization, and integrated discovery (DAVID) [8] to understand the biological implications of the outcomes.

Results

Based on the Blastn analysis, 124 hits or overlapping sequences were observed in the analysis of H1N1 vs. Homosapiens. 287 hits were observed between the overlapping segments of Streptococcus pneumoniae and Homo sapiens. The results are published in the data repository (supplement data 1 and 2). DAVID analysis showed various gene enrichment related to functions with statistical significance. The results are published in the supplement data repository (supplement data 3). The enrichment values and the level of significance of the genes are also shown in the results. A wide range of enrichment and functional annotations are observed, which give insights into the background processes after the vaccinations or infections with these organisms. The functional annotation chart with biogrid interactions (Figure 1), genes and pathway map (Figure 2), protein domain (Figure 3) and tissue characterisation (Figure 4) derived from DAVID analysis between influenza H1N1 and Homo sapiens indicate the various functional associations with associated genes. Similarly the results of DAVID analysis with Streptococcus pneumoniae and Homo sapiens show the associated protein domain (Figure 5), pathways (Figure 6), genes associated with tissue expression (Figure 7) and biogrid interactions (Supplement Figure S1).
Numerically streptococcus pneumoniae has more functional interactions than influenza H1N1 virus though the extent of biological outcomes is difficult to quantify. NDEx analysis of the overlapping genes showed the pathways associated with the genes and gene ontology analysis (Figure 8 and Figure 9) showed the relevant associated genes (Supplement Figures S2 and S3). Heat shock related pathways and signalling was predominantly involved with S. pneumoniae-homo sapiens overlapping genes (Figure 9). Genes related to histone modifications, myc pathways, DNA damage check point signalling, FGF/IGF, notch signalling were associated with influenza – Homo sapiens overlap related genes (Supplement Figure S2). PRKN, SNCA, STUB1, GPR37, SEPT, TUBA, TUBB genes related pathways concerning proteasomal degradation were associated with S. pneumonia-Homo sapiens overlapping genes (Supplement Figure S3). Some of the other seen by pathway figures similarity were KRAS, EGFR and by INDRO GO similarity ELAVL1 and MAPKAPK2 were some of the pathways identified (Supplement Figure S4) when analysed between influenza H1N1 Vs Homosapiens. Genes like HSF1, GCase and HSPA9 were some of the pathways identified when analysed between Streptococcus pneumoniae Vs Homosapiens (Supplement Figure S5).

Discussion

In the comparison of the nucleotide sequences, there were many overlapping significant alignments between the influenza (H1N1) and Streptococcus pneumonia and the human genome. This could be an evolutionary or a survival process where the organisms function and induce immunological processes by molecular mimicry. This can lead to the induction of cellular processes – cytoplasmic, nuclear, and various levels as seen through functional analysis with DAVID. These vaccinations are associated with various benefits, as reported by previous studies. These vaccinations are protective against diseases like Covid-19 through changes in adaptive immunity and are also reported to have cardioprotective effects though the exact mechanisms are not understood [9]. The countries which had high influenza or lower respiratory tract infections burden illnesses and countries which had higher influenza vaccinations, like South Korea, had significantly lower Covid 19 mortality during the pandemic [10]. Various pathways and genes are associated with the overlapping gene. Predominantly these are inflammation, death signalling and pathways related to epigenetic modifications. Heat shock proteins are involved in normal and other cellular activities during stress, inflammation, etc. They are targets for cancer therapy, inflammation, myocardial ischemia, transplantation, and neurodegenerative diseases’ activity modulation [11].
The PRKN gene is actively involved in the Parkin protein, which actively breaks down unnecessary proteins by tagging the damaged and excessive proteins with ubiquitin. Mutations in PRKN genes are well-established causes of early-onset parkinsonism [12]. TUBB, TUBA are microtubule related genes, SEPT genes are related to specific polymerisation during mitosis. The CHIP protein coded by the STUB1 gene binds and inhibits ATPase activity of the chaperone proteins HSC70 and HSP70 and prevent their forward reactions [13]. Alpha-synuclein is a protein encoded by SNCA and defects in this are associated with parkinsonism disease.GPR37 encodes [14] G-protein coupled receptor protein and it has been shown to interact with HSPA1A and Parkin(ligase). GPR37 are receptors for glial and neuroprotective factors [15].
As seen in Figure 8, extracellular structure organization ITGBF, LAMA2, LAMB2, ITG A3 and ITG B5; positive regulation of cell motility through Akt1, PLCG1 pathways; regulatory region DNA binding through NFKB1, mTOR, SMAD4, EGR1 pathways; and PRPF, SRSF 1/11, CSTF pathways associated with RNA processing are some of the actively involved in cellular pathways related genes associated with influenza-homo sapiens overlap associated genes. The AKT pathway has a significant role in interacting with oncogenes and also metabolic pathways [16]. Higher PLCG1 is associated with tumour growth and poor survival [17].
MAPKAPK2 is involved in various cellular pathways involved in stress and inflammation, nuclear export, and gene expression regulation. It plays an important role in tumour regulation [18,19]. ELAVL1 primarily couples mRNA stability with the 3’ UTSs of interferon-stimulated genes [20]. The EGFR signalling pathway is one of the most important pathways in mammalian cells, which regulates a series of important events, including proliferation, migration, differentiation, and apoptosis, as well as those that regulate intercellular communication during development. EGFR is a major gene in the pathogenesis of lung cancer [21].
KRAS-related genes are involved in cellular growth, division, survival, and death. KRAS is also a target of active research for its regulatory molecular identification [22]. HSF1 is a major transcription factor for heat shock proteins. HSPA9 belongs to HSP 70 gene family. This plays a role in cellular proliferation, stress response, and maintenance of mitochondria. HSPA9 is active in regulating apoptosis also. HSP 27 was shown to be a substrate of this kinase in vivo [23]. GCase catalyzes the cleavage of major glycolipid glucosylceramide (GL-1) into glucose and ceramide and the minor lipid glucosphingosine into sphingosine and water [24].
Further studies involving the protein encoded by these overlapping nucleotide sequences would provide more information about the changes or induction of the cellular functions. Similarly, other closely associated microorganisms like commensals can also be studied to better understand the cause-effect/associations of various disease pathology in humans, such as autoimmune disorders. Incidence of non-communicable diseases like coronary artery disease, diabetes, etc., is also interesting to study if there is any influence by the microbiological changes.

Conclusion

The study shows overlapping nucleotide sequences between the human genome and Streptococcus pneumoniae and Influenza (H1N1) virus genome sequences. These overlapping sequences are also associated with various functional annotations. Further evaluations can help to understand the modifications of the encoded proteins and metabolism during these infections.

Supplementary Materials

The following supporting information can be downloaded at the website of this paper posted on Preprints.org.

Author Contributions

MCA conceived the idea, performed the analysis in DAVID and NDEx, and wrote the paper. JW, JL, RH performed the Blastn analysis and derived the results in Blastn.

Funding

None.

Conflicts of Interest

None.

References

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Figure 1. Influenza H1N1 virus Vs. Homosapiens - Biogrid interactions. Influenza H1N1 virus Vs. Homo sapiens – functional annotation chart with biogrid interactions by DAVID analysis.
Figure 1. Influenza H1N1 virus Vs. Homosapiens - Biogrid interactions. Influenza H1N1 virus Vs. Homo sapiens – functional annotation chart with biogrid interactions by DAVID analysis.
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Figure 2. Influenza H1N1 virus Vs. Homosapiens – pathways. Influenza H1N1 virus Vs. Homo sapiens – genes in pathway map.
Figure 2. Influenza H1N1 virus Vs. Homosapiens – pathways. Influenza H1N1 virus Vs. Homo sapiens – genes in pathway map.
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Figure 3. Influenza H1N1 virus Vs. Homosapiens - Protein domains. Influenza H1N1 virus Vs. Homo sapiens – functional protein domains.
Figure 3. Influenza H1N1 virus Vs. Homosapiens - Protein domains. Influenza H1N1 virus Vs. Homo sapiens – functional protein domains.
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Figure 4. Influenza H1N1 virus Vs. Homosapiens – Tissue expressions. Influenza H1N1 virus Vs. Homo sapiens - tissue expressions.
Figure 4. Influenza H1N1 virus Vs. Homosapiens – Tissue expressions. Influenza H1N1 virus Vs. Homo sapiens - tissue expressions.
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Figure 5. Streptococcus pneumoniae Vs. Homo sapiens - protein domain. Streptococcus pneumoniae Vs. Homo sapiens – functional protein domain.
Figure 5. Streptococcus pneumoniae Vs. Homo sapiens - protein domain. Streptococcus pneumoniae Vs. Homo sapiens – functional protein domain.
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Figure 6. Streptococcus pneumoniae Vs. Homo sapiens – genes and pathways. Streptococcus pneumonia Vs. Homo sapiens – genes in pathway map.
Figure 6. Streptococcus pneumoniae Vs. Homo sapiens – genes and pathways. Streptococcus pneumonia Vs. Homo sapiens – genes in pathway map.
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Figure 7. Streptococcus pneumoniae Vs. Homo sapiens - tissue expressions.
Figure 7. Streptococcus pneumoniae Vs. Homo sapiens - tissue expressions.
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Figure 8. Gene ontology and pathway analysis through NDEx – Influenza virus Vs. Homo sapiens.
Figure 8. Gene ontology and pathway analysis through NDEx – Influenza virus Vs. Homo sapiens.
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Figure 9. Gene ontology and pathway analysis through NDEx – Streptococcus pneumoniae Vs. Homo sapiens.
Figure 9. Gene ontology and pathway analysis through NDEx – Streptococcus pneumoniae Vs. Homo sapiens.
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