A novel method addressing NGS-based mappability bias for sensitive detection of DNA alterations.

A turning point in cancer research is the introduction of massively parallel sequencing technology which greatly reduced the cost and time for genome sequencing. This enhanced the scope for detecting and analyzing the role of structural alterations in cancer. However, certain bias exists in NGS-based approaches, which badly affects the CNV identification process. Moreover, DNA repeats existing in CNV regions need special attention as they will degrade the performance of majority of the existing CNV detection tools, even after applying generalized bias correction method. This motivated this work, where a novel method has been designed to address the issue of DNA repeats and thereby mappability bias existing in regions of CNV. The method consists of three phases, where the first phase computes the alignment information of uniquely mapped DNA reads, considering the base quality and base mismatch parameters at nucleotide level precision. The second and the third phase use a novel approach to allocate the non-uniquely mapped reads to an optimal region of the DNA repeats based on a probabilistic membership model. The proposed method is capable of identifying CNVs present in coding, as well as non-coding region of the DNA, and is also capable of detecting CNVs existing in DNA repeat regions. The methodology achieves a sensitivity greater than [Formula: see text] during the performed simulations, and on real data, the detected variants are validated with the database of genomic variants, where the percentage overlap is also greater than 95%, and has achieved much better breakpoint prediction, as compared with other popular bias correction CNV detection methods.

Treatment of Menstrual Irregularities with Individualized Homeopathic Medicinal Products in Early Reproductive Females: A Double-Blind, Randomized, Placebo-Controlled Trial.

Objectives: Prevalence of irregular menstrual cycle ranges from 81.7% to 96.3%. Recent research suggested that homeopathy is one of the most popular choices for women with various gynecological disorders. This trial was aimed at differentiating individualized homeopathic medicinal products (IHMPs) from identical-looking placebos in the treatment of menstrual irregularities in early reproductive women. Design: Double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: D. N. De Homoeopathic Medical College & Hospital, Kolkata, West Bengal, India. Subjects: Ninety-two females with menstrual irregularities. Interventions: Group verum (n = 46; IHMPs plus concomitant care) versus group control (n = 46; placebos plus concomitant care). Outcome Measures: Primary-The proportion of early reproductive females in whom menstrual irregularities can be corrected for consecutive three cycles; Secondary-Menstrual Distress Questionnaire (MDQ) total score; all of them were measured at baseline and every month, up to 4 months. Results: Intention-to-treat sample (n = 92) was analyzed. Group differences were examined by chi-squared tests with categorical outcomes, two-way repeated measure analysis of variance accounting for the time-effect interactions, and unpaired t-tests comparing the mean estimates obtained individually every month. The level of significance was set at p < 0.05 two-tailed. After 4 months of intervention, the group difference in the primary outcome was nonsignificant statistically-IHMPs: 22/46 v/s placebo: 24/46, chi-square (Yates corrected) = 0.043, p = 0.835. The improvement observed in the MDQ total score (F1,90 = 0.054, p = 0.816) and subscales scores were higher in the IHMPs group than in placebos, however statistically nonsignificant in most of the occasions, except for the behavioral change subscale (F1,90 = 0.029, p < 0.001). Pulsatilla nigricans was the most frequently prescribed medicine. Kent's Repertory and Zandvoort's Complete Repertory were the most frequently used repertories. No harm or serious adverse events were reported from either group. Conclusions: The analysis failed to demonstrate clearly that IHMPs were effective beyond placebos in all but one of the outcomes. More appropriate outcome measures may be sought for future trials. Clinical Trial Registration Number: CTRI/2022/04/041659.