Does Logarithm Transformation of Microarray Data Affect Ranking Order of Differentially Expressed Genes?

A common practice in microarray analysis is to transform the microarray raw data (light intensity) by a logarithmic transformation, and the justification for this transformation is to make the distribution more symmetric and Gaussian-like. Since this transformation is not universally practiced in all microarray analysis, we examined whether the discrepancy of this treatment of raw data affect the "high level" analysis result. In particular, whether the differentially expressed genes as obtained by $t$-test, regularized t-test, or logistic regression have altered rank orders due to presence or absence of the transformation. We show that as much as 20%--40% of significant genes are "discordant" (significant only in one form of the data and not in both), depending on the test being used and the threshold value for claiming significance. The t-test is more likely to be affected by logarithmic transformation than logistic regression, and regularized $t$-test more affected than t-test. On the other hand, the very top ranking genes (e.g. up to top 20--50 genes, depending on the test) are not affected by the logarithmic transformation.Comment: submitted to IEEE/EMBS Conference'0

Effective charge and free energy of DNA inside an ion channel

Translocation of a single stranded DNA (ssDNA) through an alpha-hemolysin channel in a lipid membrane driven by applied transmembrane voltage V was extensively studied recently. While the bare charge of the ssDNA piece inside the channel is approximately 12 (in units of electron charge) measurements of different effective charges resulted in values between one and two. We explain these challenging observations by a large self-energy of a charge in the narrow water filled gap between ssDNA and channel walls, related to large difference between dielectric constants of water and lipid, and calculate effective charges of ssDNA. We start from the most fundamental stall charge $q_s$, which determines the force $F_s= q_s V/L$ stalling DNA against the voltage V (L is the length of the channel). We show that the stall charge $q_s$ is proportional to the ion current blocked by DNA, which is small due to the self-energy barrier. Large voltage V reduces the capture barrier which DNA molecule should overcome in order to enter the channel by $|q_c|V$, where $q_c$ is the effective capture charge. We expressed it through the stall charge $q_s$. We also relate the stall charge $q_s$ to two other effective charges measured for ssDNA with a hairpin in the back end: the charge $q_u$ responsible for reduction of the barrier for unzipping of the hairpin and the charge $q_e$ responsible for DNA escape in the direction of hairpin against the voltage. At small V we explain reduction of the capture barrier with the salt concentration.Comment: Typos are correcte

Sensitivity dependent model of protein-protein interaction networks

The scale free structure p(k)~k^{-gamma} of protein-protein interaction networks can be reproduced by a static physical model in simulation. We inspect the model theoretically, and find the key reason for the model to generate apparent scale free degree distributions. This explanation provides a generic mechanism of "scale free" networks. Moreover, we predict the dependence of gamma on experimental protein concentrations or other sensitivity factors in detecting interactions, and find experimental evidence to support the prediction.Comment: organization improved, and experimental evidence of predicted dependence on sensitivity is addresse

On canonical bundle formula for fibrations of curves with arithmetic genus one

In this paper, we develop canonical bundle formulas for fibrations of relative dimension one in characteristic $p>0$. For such a fibration from a log pair $f\colon (X, \Delta) \to S$, if $f$ is separable, we can obtain a formula similar to the one due to Witaszek \cite{Wit21}; if $f$ is inseparable, we treat the case when $S$ is of maximal Albanese dimension. As an application, we prove that for a klt pair $(X,\Delta)$ with $-(K_X+\Delta)$ nef, if the Albanese morphism $a_X\colon X \to A$ is of relative dimension one, then $X$ is a fiber space over $A$

PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors.

Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL phosphorylation in a positive feedback loop. Furthermore, deletion of PUMA partially rescues necroptosis-mediated developmental defects in FADD-deficient embryos. Collectively, our results reveal a signal amplification mechanism mediated by PUMA and cytosolic DNA sensors that is involved in TNF-driven necroptotic death in vitro and in vivo

Constraints imposed by non-functional protein–protein interactions on gene expression and proteome size

Crowded intracellular environments present a challenge for proteins to form functional specific complexes while reducing non-functional interactions with promiscuous non-functional partners. Here we show how the need to minimize the waste of resources to non-functional interactions limits the proteome diversity and the average concentration of co-expressed and co-localized proteins. Using the results of high-throughput Yeast 2-Hybrid experiments, we estimate the characteristic strength of non-functional protein–protein interactions. By combining these data with the strengths of specific interactions, we assess the fraction of time proteins spend tied up in non-functional interactions as a function of their overall concentration. This allows us to sketch the phase diagram for baker's yeast cells using the experimentally measured concentrations and subcellular localization of their proteins. The positions of yeast compartments on the phase diagram are consistent with our hypothesis that the yeast proteome has evolved to operate closely to the upper limit of its size, whereas keeping individual protein concentrations sufficiently low to reduce non-functional interactions. These findings have implication for conceptual understanding of intracellular compartmentalization, multicellularity and differentiation

Microbial diversity and physicochemical properties in farmland soils amended by effective microorganisms and fulvic acid for cropping Asian ginseng

Demand for products made from the dry mass of Asian ginseng (Panax ginseng) is growing, but harvest is limited by fungal disease infection when ginseng is replanted in the same field. Rotated cropping with maize can cope with the replant limit, but it may take decades. We aimed to amend post-maize-cropping farmland soils for cultivating Asian ginseng, using effective microorganisms EMs and fulvic acid (FA) additives and detecting and comparing their effects on soil microbial diversity and physiochemical properties. Amendments promoted seedling survival and depressed disease-infection. Both EMs and FA increased the relative abundances of Pseudomonas, Flavobacterium, Duganella, and Massilia spp., but, decreased the relative abundances of Fusarium and Sistotrema. In addition, soil nutrient availability and properties that benefitted nutrient availabilities were promoted. In conclusion, amendments with EMs and FA improved the fertility of farmland soils, and the quality of Asian ginseng, and revealed the relationship between soil microbial diversity and physiochemical properties

Self-energy limited ion transport in sub-nanometer channels

The current-voltage characteristics of the alpha-Hemolysin protein pore during the passage of single-stranded DNA under varying ionic strength, C, are studied experimentally. We observe strong blockage of the current, weak super-linear growth of the current as a function of voltage, and a minimum of the current as a function of C. These observations are interpreted as the result of the ion electrostatic self-energy barrier originating from the large difference in the dielectric constants of water and the lipid bilayer. The dependence of DNA capture rate on C also agrees with our model.Comment: more experimental material is added. 4 pages, 7 figure