Category: Nevin Manimala

Bioinformatics. 2023 Jan 1;39(1):btad016. doi: 10.1093/bioinformatics/btad016.

ABSTRACT

MOTIVATION: Binary (or Boolean) matrices provide a common effective data representation adopted in several domains of computational biology, especially for investigating cancer and other human diseases. For instance, they are used to summarize genetic aberrations-copy number alterations or mutations-observed in cancer patient cohorts, effectively highlighting combinatorial relations among them. One of these is the tendency for two or more genes not to be co-mutated in the same sample or patient, i.e. a mutual-exclusivity trend. Exploiting this principle has allowed identifying new cancer driver protein-interaction networks and has been proposed to design effective combinatorial anti-cancer therapies rationally. Several tools exist to identify and statistically assess mutual-exclusive cancer-driver genomic events. However, these tools need to be equipped with robust/efficient methods to sort rows and columns of a binary matrix to visually highlight possible mutual-exclusivity trends.

RESULTS: Here, we formalize the mutual-exclusivity-sorting problem and present MutExMatSorting: an R package implementing a computationally efficient algorithm able to sort rows and columns of a binary matrix to highlight mutual-exclusivity patterns. Particularly, our algorithm minimizes the extent of collective vertical overlap between consecutive non-zero entries across rows while maximizing the number of adjacent non-zero entries in the same row. Here, we demonstrate that existing tools for mutual-exclusivity analysis are suboptimal according to these criteria and are outperformed by MutExMatSorting.

AVAILABILITY AND IMPLEMENTATION: https://github.com/AleVin1995/MutExMatSorting.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:36669133 | DOI:10.1093/bioinformatics/btad016

Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2217902120. doi: 10.1073/pnas.2217902120. Epub 2023 Jan 20.

ABSTRACT

Sex-biased humoral immune responses to COVID-19 patients have been observed, but the cellular basis for this is not understood. Using single-cell proteomics by mass cytometry, we find disrupted regulation of humoral immunity in COVID-19 patients, with a sex-biased loss of circulating follicular regulatory T cells (cTfr) at a significantly greater rate in male patients. In addition, a male sex-associated cellular network of T-peripheral helper, plasma blasts, proliferating and extrafollicular/atypical CD11c⁺ memory B cells was strongly positively correlated with neutralizing antibody concentrations and negatively correlated with cTfr frequency. These results suggest that sex-specific differences to the balance of cTfr and a network of extrafollicular antibody production-associated cell types may be a key factor in the altered humoral immune responses between male and female COVID-19 patients.

PMID:36669118 | DOI:10.1073/pnas.2217902120

Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2212252120. doi: 10.1073/pnas.2212252120. Epub 2023 Jan 20.

ABSTRACT

Pain typically evolves over time, and the brain needs to learn this temporal evolution to predict how pain is likely to change in the future and orient behavior. This process is termed temporal statistical learning (TSL). Recently, it has been shown that TSL for pain sequences can be achieved using optimal Bayesian inference, which is encoded in somatosensory processing regions. Here, we investigate whether the confidence of these probabilistic predictions modulates the EEG response to noxious stimuli, using a TSL task. Confidence measures the uncertainty about the probabilistic prediction, irrespective of its actual outcome. Bayesian models dictate that the confidence about probabilistic predictions should be integrated with incoming inputs and weight learning, such that it modulates the early components of the EEG responses to noxious stimuli, and this should be captured by a negative correlation: when confidence is higher, the early neural responses are smaller as the brain relies more on expectations/predictions and less on sensory inputs (and vice versa). We show that participants were able to predict the sequence transition probabilities using Bayesian inference, with some forgetting. Then, we find that the confidence of these probabilistic predictions was negatively associated with the amplitude of the N2 and P2 components of the vertex potential: the more confident were participants about their predictions, the smaller the vertex potential. These results confirm key predictions of a Bayesian learning model and clarify the functional significance of the early EEG responses to nociceptive stimuli, as being implicated in confidence-weighted statistical learning.

PMID:36669115 | DOI:10.1073/pnas.2212252120

Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2207516120. doi: 10.1073/pnas.2207516120. Epub 2023 Jan 20.

ABSTRACT

The adaptive immune system is a diverse ecosystem that responds to pathogens by selecting cells with specific receptors. While clonal expansion in response to particular immune challenges has been extensively studied, we do not know the neutral dynamics that drive the immune system in the absence of strong stimuli. Here, we learn the parameters that underlie the clonal dynamics of the T cell repertoire in healthy individuals of different ages, by applying Bayesian inference to longitudinal immune repertoire sequencing (RepSeq) data. Quantifying the experimental noise accurately for a given RepSeq technique allows us to disentangle real changes in clonal frequencies from noise. We find that the data are consistent with clone sizes following a geometric Brownian motion and show that its predicted steady state is in quantitative agreement with the observed power-law behavior of the clone-size distribution. The inferred turnover time scale of the repertoire increases with patient age and depends on the clone size in some individuals.

PMID:36669107 | DOI:10.1073/pnas.2207516120

Am J Dermatopathol. 2023 Feb 1;45(2):99-106. doi: 10.1097/DAD.0000000000002335. Epub 2022 Dec 7.

ABSTRACT

INTRODUCTION: Leprosy is an ancient and chronic infectious disease caused by 2 mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). Recently, our research group observed that HES-1, an innate cellular component of the Notch signaling pathway, is related to the pathogenesis of leprosy. Therefore, it could be helpful in its detection.

OBJECTIVE: To determine the expression of HES-1 in the skin of patients with paucibacillary (PB) leprosy.

METHODS: A cross-sectional, descriptive, observational study was conducted. Forty-five skin samples from patients with leprosy were evaluated (30 samples from MB leprosy and 15 from PB leprosy) using immunohistochemistry of HES-1 and S-100.

RESULTS: PB leprosy biopsies revealed a reduction of HES-1 in 66.7% of the epidermis, 80% of the eccrine glands, and 62.5% of the hair follicles of these patients, with statistical differences in the control group (P < 0.0001). Besides, HES-1 showed similar utility to S-100 immunostaining in detecting the MB and PB leprosy.

CONCLUSIONS: HES-1 is a transcriptional factor also reduced in PB patients’ epidermis and skin appendages. Finally, our data show that HES-1 could be a biomarker in diagnosing PB and MB leprosy.

PMID:36669073 | DOI:10.1097/DAD.0000000000002335

Vet Sci. 2023 Jan 16;10(1):64. doi: 10.3390/vetsci10010064.

ABSTRACT

Housing confinement, adaptation to different light/dark conditions, and social deprivation could modify the amount of total locomotor behavior of calves recommended for their psychophysical health. Total locomotor behavior was recorded by means of an activity data logger every 5 min for 6 consecutive days. To do that eight clinically healthy 30-day-old Holstein calves living in calf boxes under natural photoperiod and environmental conditions were enrolled. ANOVA (analysis of variance) showed a statistical effect of the day of monitoring and animal. In the temporal distribution of the resting-activity frequency, it was observed that the calves presented periods of total locomotor behavior with the existence of two peaks, one between 06:00-07:00 and another between 17:00-18:00, which corresponds to time of food intake. In all animals, a diurnal daily rhythm of total locomotor behavior was observed during time of monitoring. Intrasubject and intersubject variabilities were statistically different in mesor, amplitude, and robustness of rhythm. In conclusion, the total locomotor behavior showed a diurnal daily rhythmicity in 30-day-old calves. The characteristics of rhythm were different from individual to individual and from day to day. The recorded intersubject variability must be taken in consideration during the monitoring of farm animals and justifies the application of the device to each animal, as precision livestock farming suggests.

PMID:36669065 | DOI:10.3390/vetsci10010064

Vet Sci. 2023 Jan 15;10(1):61. doi: 10.3390/vetsci10010061.

ABSTRACT

First cannulation is a critical manoeuvre in equine laparoscopy. This retrospective study aimed at the comparison of the frequency and type of complications detected when using different human laparoscopy devices for laparoscopic access in standing horses, and the influence of body condition in such complications. Forty-four procedures were included, and retrieved data comprised cannula insertion technique, body condition, and type and frequency of complications. Laparoscopic access techniques were classified into five groups: P: pneumoperitoneum created using Veress needle prior to cannulation; T: sharp trocar; D: direct access via surgical incision; V: Visiport optical trocar and H: optical helical cannula (OHC). In groups T, D, V and H, access was achieved without prior induction of pneumoperitoneum. Complications were registered in 13/44 procedures, of which retroperitoneal insufflation was the most common (6/13). Statistically significant association was found between the complication incidence and the type of access, with group D showing the highest complication frequency (80%) and group H the lowest frequency (0%). The majority of complications (9/13) were observed in overweight horses. We conclude that devices designed for human patients can be used for laparoscopic access in standing horses, with the use of OHC minimizing the appearance of complications, especially in overweight horses with OW.

PMID:36669062 | DOI:10.3390/vetsci10010061

Vet Sci. 2023 Jan 7;10(1):43. doi: 10.3390/vetsci10010043.

ABSTRACT

The aim of this study was to investigate the influence of calving-related injuries of the vestibulum vaginae and the vagina on fertility measures in heifers. German Holstein heifers (n = 236) were checked for vestibulum vaginae and vaginal injuries. These were scored according to localization, depth and length. The healing process was assessed until day 42 post partum. Calving ease and the occurrence of metritis and endometritis were evaluated. In 160 heifers, the following fertility measures were calculated to assess the reproductive performance of heifers: mean interval from calving to first insemination, mean days open, mean interval from first insemination to conception, mean calving interval, mean pregnancy index, percentage of animals pregnant at 200 days p.p., and first service conception rate. On the one hand, dystocia was a risk factor for injuries of the soft birth canal, and, on the other hand, those injuries were a risk factor for metritis and endometritis. In this study, calving-related injuries of the vestibulum vaginae and the vagina had no statistically significant effect on the reproductive performance of heifers. One reason for this outcome was probably the overall good healing tendencies of those injuries in heifers.

PMID:36669045 | DOI:10.3390/vetsci10010043

Vet Sci. 2022 Dec 24;10(1):9. doi: 10.3390/vetsci10010009.

ABSTRACT

Farm animals behavior research uses video cameras, mainly for visual observation and recording. The purpose of this feasibility study was to enrich the predictable methods of boar semen production capacity by correlating sperm variables with the scrotal contractions (SC) frequency and intensity. A video camera was used to record the reaction of the scrotum during ejaculation. The respective collected ejaculates were evaluated and semen parameters, such as viability, morphology, membranes functional integrity and kinematics, were determined. The camera recorded the scrotal contractions/relaxations and the video was handled by the Image Processing Toolbox of Matlab (Mathworks Inc., Natick, MA, USA). The SC intensity was verified as a percentage change in the scrotum size among the video frames of maximum contraction and relaxation. The archived data from the frames were analyzed statistically, using a linear mixed effects model that involved sperm assessed parameters. Correlations of the SC intensity with the average path velocity, VAP (R² = 0.591, p = 0.043) and with the percentage of the cytoplasmic droplets (R² = 0.509, p = 0.036) were noticed. Previous studies reported the positive correlation of VAP with the number of live-born piglets. In conclusion, video monitoring of the boar scrotal function during ejaculation is useful, but more research is needed to establish its appropriateness as a supplementary method for the prognosis of boar ability to produce high-quality semen.

PMID:36669010 | DOI:10.3390/vetsci10010009

Diabetes. 2023 Feb 1;72(2):175-183. doi: 10.2337/db22-0110.

ABSTRACT

In this study we examine the instrument selection strategies currently used throughout the type 2 diabetes and HbA1c Mendelian randomization (MR) literature. We then argue for a more integrated and thorough approach, providing a framework to do this in the context of HbA1c and diabetes. We conducted a literature search for MR studies that have instrumented diabetes and/or HbA1c. We also used data from the UK Biobank (UKB) (N = 349,326) to calculate instrument strength metrics that are key in MR studies (the F statistic for average strength and R2 for total strength) with two different methods (“individual-level data regression” and Cragg-Donald formula). We used a 157-single nucleotide polymorphism (SNP) instrument for diabetes and a 51-SNP instrument (with partition into glycemic and erythrocytic as well) for HbA1c. Our literature search yielded 48 studies for diabetes and 22 for HbA1c. Our UKB empirical examples showed that irrespective of the method used to calculate metrics of strength and whether the instrument was the main one or included partition by function, the HbA1c genetic instrument is strong in terms of both average and total strength. For diabetes, a 157-SNP instrument was shown to have good average strength and total strength, but these were both substantially lesser than those of the HbA1c instrument. We provide a careful set of five recommendations to researchers who wish to genetically instrument type 2 diabetes and/or HbA1c. In MR studies of glycemia, investigators should take a more integrated approach when selecting genetic instruments, and we give specific guidance on how to do this.

PMID:36669000 | DOI:10.2337/db22-0110