Distribution-Free Model-Agnostic Regression Calibration via Nonparametric Methods

In this paper, we consider the uncertainty quantification problem for regression models. Specifically, we consider an individual calibration objective for characterizing the quantiles of the prediction model. While such an objective is well-motivated from downstream tasks such as newsvendor cost, the existing methods have been largely heuristic and lack of statistical guarantee in terms of individual calibration. We show via simple examples that the existing methods focusing on population-level calibration guarantees such as average calibration or sharpness can lead to harmful and unexpected results. We propose simple nonparametric calibration methods that are agnostic of the underlying prediction model and enjoy both computational efficiency and statistical consistency. Our approach enables a better understanding of the possibility of individual calibration, and we establish matching upper and lower bounds for the calibration error of our proposed methods. Technically, our analysis combines the nonparametric analysis with a covering number argument for parametric analysis, which advances the existing theoretical analyses in the literature of nonparametric density estimation and quantile bandit problems. Importantly, the nonparametric perspective sheds new theoretical insights into regression calibration in terms of the curse of dimensionality and reconciles the existing results on the impossibility of individual calibration. To our knowledge, we make the first effort to reach both individual calibration and finite-sample guarantee with minimal assumptions in terms of conformal prediction. Numerical experiments show the advantage of such a simple approach under various metrics, and also under covariates shift. We hope our work provides a simple benchmark and a starting point of theoretical ground for future research on regression calibration.Comment: Accepted at NeurIPS 2023 and update a camera-ready version; Add some experiments and literature review

Circulating Lysophosphatidylcholines in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women.

ObjectivesThis study aimed to explore associations of lysophosphatidylcholines (LPCs) in early pregnancy with gestational diabetes mellitus (GDM), and whether LPCs mediated the associations of bile acids with GDM risk or had interactive effects with bile acids on GDM risk.DesignWe conducted a 1:1 nested case-control study (n = 486) from a large prospective pregnant women cohort in urban Tianjin, China. Blood samples were collected at their first antenatal care visit (median at 10th gestational week). LPCs were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional binary logistic regression and restricted cubic spline analysis were used to identify cutoff points of these metabolites for GDM risk.ResultsOf the 6 detectable LPCs, LPC14:0 less than 0.24 nmol/mL, LPC15:0 at 0.45 nmol/mL or greater, and LPC18:0 at 18.00 nmol/mL or greater were independently associated with GDM risk. Adjustment for LPC18:0 slightly attenuated odds ratios (ORs) of deoxycholic acid (DCA, ≤ 0.36 nmol/mL) and glycoursodeoxycholic acid (GUDCA, ≤ 0.07 nmol/mL) for GDM, and the correlations of DCA and GUDCA with LPC18:0 were weak. However, the presence of DCA at 0.36 nmol/mL or less greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 8.18 (2.51-26.7) up to 17.7 (6.64-47.1), with significant additive interaction. Similarly, the presence of GUDCA at 0.07 nmol/mL or less also greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 17.2 (1.77-168) up to 73.8 (12.7-429), with significant additive interaction.ConclusionsLPCs in early pregnancy were associated with GDM risk. Low DCA or GUDCA greatly amplified the effect of high LPC18:0 on GDM, and its molecular mechanism is worth further investigations

Dietary specialization drives multiple independent losses and gains in the bitter taste gene repertoire of Laurasiatherian Mammals

Background: Bitter taste perception is essential for species with selective food intake, enabling them to avoid unpalatable or toxic items. Previous studies noted a marked variation in the number of TAS2R genes among various vertebrate species, but the underlying causes are not well understood. Laurasiatherian mammals have highly diversified dietary niche, showing repeated evolution of specialized feeding preferences in multiple lineages and offering a unique chance to investigate how various feeding niches are associated with copy number variation for bitter taste receptor genes. Results: Here we investigated the evolutionary trajectories of TAS2Rs and their implications on bitter taste perception in whole-genome assemblies of 41 Laurasiatherian species. The number of intact TAS2Rs copies varied considerably, ranging from 0 to 52. As an extreme example of a narrow dietary niche, the Chinese pangolin possessed the lowest number of intact TAS2Rs (n = 2) among studied terrestrial vertebrates. Marine mammals (cetacea and pinnipedia), which swallow prey whole, presented a reduced copy number of TAS2Rs (n = 0-5). In contrast, independent insectivorous lineages, such as the shrew and insectivorous bats possessed a higher TAS2R diversity (n = 52 and n = 20-32, respectively), exceeding that in herbivores (n = 9-22) and omnivores (n = 18-22). Conclusions: Besides herbivores, insectivores in Laurasiatheria tend to have more functional TAS2Rs in comparison to carnivores and omnivores. Furthermore, animals swallowing food whole (cetacean, pinnipedia and pangolin) have lost most functional TAS2Rs. These findings provide the most comprehensive view of the bitter taste gene repertoire in Laurasiatherian mammals to date, casting new light on the relationship between losses and gains of TAS2Rs and dietary specialization in mammals

RNASEL and MIR146A SNP-SNP Interaction as a Susceptibility Factor for Non-Melanoma Skin Cancer

Immunity and inflammatory pathways are important in the genesis of non-melanoma skin cancers (NMSC). Functional genetic variation in immune modulators has the potential to affect disease etiology. We investigated associations between common variants in two key regulators, MIR146A and RNASEL, and their relation to NMSCs. Using a large population-based case-control study of basal cell (BCC) and squamous cell carcinoma (SCC), we investigated the impact of MIR146A SNP rs2910164 on cancer risk, and interaction with a SNP in one of its putative targets (RNASEL, rs486907). To examine associations between genotype and BCC and SCC, occurrence odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using unconditional logistic regression, accounting for multiple confounding factors. We did not observe an overall change in the odds ratios for SCC or BCC among individuals carrying either of the RNASEL or MIR146A variants compared with those who were wild type at these loci. However, there was a sex-specific association between BCC and MIR146A in women (ORGC = 0.73, [95%CI = 0.52–1.03]; ORCC = 0.29, [95% CI = 0.14–0.61], p-trend\u3c0.001), and a reduction in risk, albeit not statistically significant, associated with RNASEL and SCC in men (ORAG = 0.88, [95%CI = 0.65–1.19]; ORAA = 0.68, [95%CI = 0.43–1.08], p-trend = 0.10). Most striking was the strong interaction between the two genes. Among individuals carrying variant alleles of both rs2910164 and rs486907, we observed inverse relationships with SCC (ORSCC = 0.56, [95%CI = 0.38–0.81], p-interaction = 0.012) and BCC (ORBCC = 0.57, [95%CI = 0.40–0.80], p-interaction = 0.005). Our results suggest that genetic variation in immune and inflammatory regulators may influence susceptibility to NMSC, and novel SNP-SNP interaction for a microRNA and its target. These data suggest that RNASEL, an enzyme involved in RNA turnover, is controlled by miR-146a and may be important in NMSC etiology

Original Article Correlation of rs1799793 polymorphism in ERCC2 and the clinical response to platinum-based chemotherapy in patients with triple negative breast cancer

Abstract: Background: Polymorphisms of DNA repair genes may affect the repair capacity of DNA damages and cause different responses towards chemotherapy. Excision repair cross-complementing group 2 (ERCC2) plays an important role in the nucleotide excision repair. Objectives: The aim of this study was to investigate the association between ERCC2 single nucleotide polymorphisms (SNPs) and the response to platinum-based chemotherapy among patients with triple negative breast cancer. Methods: In total, 60 triple negative breast cancer patients treated with platinum-based chemotherapy were studied. The clinical, pathological and treatment data of them were collected. Sequenom's MassARRAY system was used in the detection of the SNPs of ERCC2. Finally, the association between genotypes and different clinical responses among patients was analyzed. All of the patients received a platinum-based chemotherapy for 4 cycles in median and achieved an overall response rate of 66.7%, showing a comparative good response towards platinum-based chemotherapy among triple negative breast cancer. Fifty-three of the 60 patients had got the results of ERCC2 rs1799793 polymorphisms after MassARRAY detection. Results: The proportion of GG genotype and GA genotype was 81.1% and 18.9% respectively. The response rate of the rs1799793 GG genotype group was 69.8%, while the GA genotype group only had a response rate of 30.0%. It turned out that the GG genotype was associated with better response towards platinum-based chemotherapy (P=0.030). Conclusions: ERCC2 rs1799793 polymorphism may be associated with the clinical sensitivity of platinum-based chemotherapy and could be a potential predictive biomarker for triple negative breast cancer patients treated with platinum compounds

Genus β human papillomaviruses and incidence of basal cell and squamous cell carcinomas of skin: population based case-control study

Objective To investigate the association between genus β human papillomaviruses and the incidence of non-melanocytic skin cancer in the general population

Population genomics of wild Chinese rhesus macaques reveals a dynamic demographic history and local adaptation, with implications for biomedical research

Background The rhesus macaque (RM, Macaca mulatta) is the most important nonhuman primate model in biomedical research. We present the first genomic survey of wild RMs, sequencing 81 geo-referenced individuals of five subspecies from 17 locations in China, a large fraction of the species’ natural distribution. Results Populations were structured into five genetic lineages on the mainland and Hainan Island, recapitulating current subspecies designations. These subspecies are estimated to have diverged 125.8 to 51.3 thousand years ago, but feature recent gene flow. Consistent with the expectation of a larger body size in colder climates and smaller body size in warmer climates (Bergman's rule), the northernmost RM lineage (M. m. tcheliensis), possessing the largest body size of all Chinese RMs, and the southernmost lineage (M. m. brevicaudus), with the smallest body size of all Chinese RMs, feature positively selected genes responsible for skeletal development. Further, two candidate selected genes (Fbp1, Fbp2) found in M. m. tcheliensis are involved in gluconeogenesis, potentially maintaining stable blood glucose levels during starvation when food resources are scarce in winter. The tropical subspecies M. m. brevicaudus showed positively selected genes related to cardiovascular function and response to temperature stimuli, potentially involved in tropical adaptation. We found 118 single-nucleotide polymorphisms matching human disease-causing variants with 82 being subspecies specific. Conclusions These data provide a resource for selection of RMs in biomedical experiments. The demographic history of Chinese RMs and their history of local adaption offer new insights into their evolution and provide valuable baseline information for biomedical investigation

Analysis and Suppression of Induced Voltage Pulsation in DC Winding of Five-Phase Wound-Field Switched Flux Machines

In wound-field (WF) switched flux (SF) (WFSF) machines, the DC winding induced voltage pulsation causes current ripple in the DC winding and challenges the DC power source, and deteriorates the control performance. In this paper, the induced voltage pulsation in DC winding of five-phase WFSF machines is analyzed and its reduction methods are proposed. The cycles per electric period of the open-circuit and armature reaction induced voltage pulsation in DC winding are derived analytically. Modifying the airgap permeance by optimizing the rotor pole arc or chamfering the rotor pole surface, and axial pairing of rotor segments having rotor pole with different arcs are used to suppress the induced voltage pulsation in DC winding, with >90% average torque maintained. Finite element results show that, by optimizing the rotor pole arc, the peak-to-peak value of the induced voltage pulsation in DC winding can be effectively suppressed to 59.59%, 30.67%, 29.99% and 43.35% for the 10-stator-pole five-phase WFSF machines with 8-, 9-, 11- and 12-rotor-pole rotors, respectively. By applying rotor pole surface shaping, the induced voltage pulsation in DC winding peak-to-peak value can be effectively suppressed to 61.76%, 45.47% and 40.21% for the 8-, 9- and 12-rotor-pole machines, respectively, while by applying axial pairing, it can be suppressed to 46.89%, 7.16%, 15.64% and 12.04%, respectively. The 10-stator-pole/12-rotor-pole WFSF machines having the original rotor, optimized rotor, chamfered rotor and axial paired rotor are prototyped and the experiments validate the analytical and finite element results