Return on investment and library complexity analysis for DNA sequencing

Thesis: S.M., Massachusetts Institute of Technology, Computation for Design and Optimization Program, 2016.Cataloged from PDF version of thesis.Includes bibliographical references (page 49).Understanding the profiles of information acquisition during DNA sequencing experiments is critical to the design and implementation of large-scale studies in medical and population genetics. One known technical challenge and cost driver in next-generation sequencing data is the occurrence of non-independent observations that are created from sequencing artifacts and duplication events from polymerase chain reaction (PCR). The current study demonstrates improved return on investment (ROI) modeling strategies to better anticipate the impact of non-independent observations in multiple forms of next-generation sequencing data. Here, a physical modeling approach based on Pó1ya urn was evaluated using both multi-point estimation and duplicate set occupancy vectors. The results of this study can be used to reduce sequencing costs by improving aspects of experimental design including sample pooling strategies, top-up events, and termination of non-informative samples.by Larson J. Hogstrom.S.M

Written distractor words influence brain activity during overt picture naming

Language production requires multiple stages of processing (e.g., semantic retrieval, lexical selection), each of which may involve distinct brain regions. Distractor words can be combined with picture naming to examine factors that influence language production. Phonologically-related distractors have been found to speed picture naming (facilitation), while slower response times and decreased accuracy (interference) generally occur when a distractor is categorically related to the target image. However, other types of semantically-related distractors have been reported to produce a facilitative effect (e.g., associative, part-whole). The different pattern of results for different types of semantically-related distractors raises the question about how the nature of the semantic relation influences the effect of the distractor. To explore the nature of these semantic effects further, we used functional MRI to examine the influence of four types of written distractors on brain activation during overt picture naming. Distractors began with the same sound, were categorically-related, part of the object to be named, or were unrelated to the picture. Phonologically-related trials elicited greater activation than both semantic conditions (categorically-related and part-whole) in left insula and bilateral parietal cortex, regions that have been attributed to phonological aspects of production and encoding, respectively. Semantic conditions elicited greater activation than phonological trials in left posterior MTG, a region that has been linked to concept retrieval and semantic integration. Overall, the two semantic conditions did not differ substantially in their functional activation which suggests a similarity in the semantic demands and lexical competition across these two conditions

Delivery Mode Affects Stability of Early Infant Gut Microbiota

© 2020 The Author(s) Mitchell et al. compare early-life infant gut microbiota by delivery mode, suggesting early colonization by Bacteroides regardless of delivery mode, but loss of Bacteroides by 2 weeks in C-section-delivered infants, whether or not exposed to the vagina in labor. Infant strains matched maternal rectal rather vaginal strains

Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life

Bacterial community acquisition in the infant gut impacts immune education and disease susceptibility. We compared bacterial strains across and within families in a prospective birth cohort of 44 infants and their mothers, sampled longitudinally in the first months of each child’s life. We identified mother-to-child bacterial transmission events and describe the incidence of family-specific antibiotic resistance genes. We observed two inheritance patterns across multiple species, where often the mother’s dominant strain is transmitted to the child, but occasionally her secondary strains colonize the infant gut. In families where the secondary strain of B. uniformis was inherited, a starch utilization gene cluster that was absent in the mother’s dominant strain was identified in the child, suggesting the selective advantage of a mother’s secondary strain in the infant gut. Our findings reveal mother-to-child bacterial transmission events at high resolution and give insights into early colonization of the infant gut

Strain-Level Analysis of Mother-to-Child Bacterial Transmission during the First Few Months of Life

Bacterial community acquisition in the infant gut impacts immune education and disease susceptibility. We compared bacterial strains across and within families in a prospective birth cohort of 44 infants and their mothers, sampled longitudinally in the first months of each child's life. We identified mother-to-child bacterial transmission events and describe the incidence of family-specific antibiotic resistance genes. We observed two inheritance patterns across multiple species, where often the mother's dominant strain is transmitted to the child, but occasionally her secondary strains colonize the infant gut. In families where the secondary strain of B. uniformis was inherited, a starch utilization gene cluster that was absent in the mother's dominant strain was identified in the child, suggesting the selective advantage of a mother's secondary strain in the infant gut. Our findings reveal mother-to-child bacterial transmission events at high resolution and give insights into early colonization of the infant gut. Using longitudinal metagenomic sequencing from 44 mother/child pairs, Yassour et al. characterized mother-to-child strain transmission patterns. While mothers' dominant strains were often inherited, nondominant secondary strain transmissions were also observed. Microbial functional analysis reveals that inherited maternal secondary strains may have a selective advantage to colonize infant guts.National Institutes of Health (Grant 1DP3DK094338–01

A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles

We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https://clue.io