Fig 2. HLH genes are significantly enriched within the SARS-CoV-2 host protein interactome.

A connectivity score was calculated for each of the genes of interest (e.g. HLH genes in this work). We further analyzed the network connectivity of all genes to the SARS-CoV2 proteins (or randomly picked genes). With these two analyses, we ended up with two lists of connectivity scores: SA (for HLH genes) and SB (for all background genes). Then, we calculated the statistical significance (p-value) using a one-sided Mann-Whitney rank test to determine whether SA is significantly smaller than SB (stronger connectivity). SA significant p-value implies that the list of proteins (genes) of interest is “significantly connected” to the SARS-CoV2 proteins. A) A list of 10 known COVID19 related genes (differential genes in severe COVID19 patients) have statistically stronger connections to the SARS-CoV-2 proteins compared with all background genes (p-value = 0.017). B) A list of 100 random genes does not “significantly” connect to the SARS-CoV-2 proteins. C) The 23 Male infertility genes do not “significantly” connect to the SARS-CoV-2 proteins. D) The 11 HLH genes have statistically (p-value = 0.00821) stronger connections to the SARS-CoV-2 proteins (compared with all background genes). E) A list of 45 vascular angiogenesis genes linked to both H1N1 and SARS-CoV-2 pulmonary infections significantly (p-value = 4.89e-5) connect to the SARS-CoV-2 proteins. The 11 HLH genes have the smallest mean/median connectivity score compared to all the gene lists analyzed. Please note that the p-values here only indicate whether the input gene lists have significantly smaller connectivity scores than all the background genes, and they could be affected by the size of the gene list. To compare the strength of the “connectivity” of input gene lists to SARS-CoV-2 proteins, we should also look at the mean (represented by a green triangle) and the median (represent by a vertical line) connectivity scores.