Although Slavic populations account for over 4.5% of world inhabitants, no centralised, open-source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for clinical genetics, biomedical research, as well as archeological and historical studies. The Polish population, which is homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a genetic reference for the Slavic nations. In this study, we analysed whole genomes of 1222 Poles to identify and genotype a wide spectrum of genomic variation, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups, and de novo variants. Common variant analyses showed that the Polish cohort is highly homogenous and shares ancestry with other European populations. In rare variant analyses, we identified 32 autosomal-recessive genes with significantly different frequencies of pathogenic alleles in the Polish population as compared to the non-Finish Europeans, including C2, TGM5, NUP93, C19orf12, and PROP1. The allele frequencies for small and structural variants, calculated for 1076 unrelated individuals, are released publicly as The Thousand Polish Genomes database, and will contribute to the worldwide genomic resources available to researchers and clinicians.

Immunotherapy is a quickly developing type of treatment and the future of therapy in oncology. This paper is a review of recent findings in the field of immunotherapy with an emphasis on immune checkpoint inhibitors. The challenges that immunotherapy might face in near future, such as primary and acquired resistance and the irAEs, are described in this article, as well as the perspectives such as identification of environmental modifiers of immunity and development of anti-cancer vaccines and combined therapies. There are multiple factors that may be responsible for immunoresistance, such as genomic factors, factors related to the immune system cells or to the cancer microenvironment, factors emerging from the host cells, as well as other factors such as advanced age, biological sex, diet, many hormones, existing comorbidities, and the gut microbiome.

COVID-19 infections pose a serious global health concern so it is crucial to identify the biomarkers for the susceptibility to and resistance against this disease that could help in a rapid risk assessment and reliable decisions being made on patients’ treatment and their potential hospitalisation. Several studies investigated the factors associated with severe COVID-19 outcomes that can be either environmental, population based, or genetic. It was demonstrated that the genetics of the host plays an important role in the various immune responses and, therefore, there are different clinical presentations of COVID-19 infection. In this study, we aimed to use variant descriptive statistics from GWAS (Genome-Wide Association Study) and variant genomic annotations to identify metabolic pathways that are associated with a severe COVID-19 infection as well as pathways related to resistance to COVID-19. For this purpose, we applied a custom-designed mixed linear model implemented into custom-written software. Our analysis of more than 12.5 million SNPs did not indicate any pathway that was significant for a severe COVID-19 infection. However, the Allograft rejection pathway (hsa05330) was significant (p = 0.01087) for resistance to the infection. The majority of the 27 SNP marking genes constituting the Allograft rejection pathway were located on chromosome 6 (19 SNPs) and the remainder were mapped to chromosomes 2, 3, 10, 12, 20, and X. This pathway comprises several immune system components crucial for the self versus non-self recognition, but also the components of antiviral immunity. Our study demonstrated that not only single variants are important for resistance to COVID-19, but also the cumulative impact of several SNPs within the same pathway matters.

Although Slavic populations account for over 3.5% of world inhabitants, no centralized, open source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for either biomedical research and genetic counseling and are essential for archeological and historical studies. Polish population, homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a good genetic reference for middle European Slavic nations.The aim of the present study was to describe first results of analyses of a newly created national database of Polish genomic variant allele frequencies. Never before has any study on the whole genomes of Polish population been conducted on such a large number of individuals (1,079).A wide spectrum of genomic variation was identified and genotyped, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups and Mendelian inconsistencies. The allele frequencies were calculated for 943 unrelated individuals and released publicly as The Thousand Polish Genomes database. A precise detection and characterisation of rare variants enriched in the Polish population allowed to confirm the allele frequencies for known pathogenic variants in diseases, such as Smith-Lemli-Opitz syndrome (SLOS) or Nijmegen breakage syndrome (NBS). Additionally, the analysis of OMIM AR genes led to the identification of 22 genes with significantly different cumulative allele frequencies in the Polish (POL) vs European NFE population. We hope that The Thousand Polish Genomes database will contribute to the worldwide genomic data resources for researchers and clinicians.