Biology subjects

Patel, T.

Publications and source records attributed to Patel, T..

3 recordsLinked to original sources

bioRxiv2018

Large differences in small RNA composition between human biofluids

Extracellular miRNAs and other small RNAs are implicated in cellular communication and may be useful as disease biomarkers. We systematically compared small RNAs in 12 human biofluid types using RNA-seq. miRNAs and tRNA-derived RNAs (tDRs) accounted for the majority of mapped reads in all biofluids, but the ratio of miRNA to tDR reads varied from 72 in plasma to 0.004 in bile. miRNA levels were highly correlated across all biofluids but levels of some miRNAs differed markedly between biofluids. tDR populations differed extensively between biofluids. Y RNA fragments were seen in all biofluids and accounted for >10% of reads in blood plasma, serum, and CSF. Reads mapping exclusively to piRNAs were very rare except in seminal plasma. These results demonstrate extensive differences in small RNAs between human biofluids and provide a useful resource for investigating extracellular RNA biology and developing biomarkers.

genomics↗

bioRxiv2017

Detecting pathogen exposure during the non-symptomatic incubation period using physiological data

Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning based method to better detect asymptomatic states during the incubation period using subtle, sub-clinical physiological markers. Starting with high-resolution physiological waveform data from non-human primate studies of viral (Ebola, Marburg, Lassa, and Nipah viruses) and bacterial (Y. pestis) exposure, we processed the data to reduce short-term variability and normalize diurnal variations, then provided these to a supervised random forest classification algorithm and post-classifier declaration logic step to reduce false alarms. In most subjects detection is achieved well before the onset of fever; subject cross-validation across exposure studies (varying viruses, exposure routes, animal species, and target dose) lead to 51h mean early detection (at 0.93 area under the receiver-operating characteristic curve [AUCROC]). Evaluating the algorithm against entirely independent datasets for Lassa, Nipah, and Y. pestis exposures un-used in algorithm training and development yields a mean 51h early warning time (at AUCROC=0.95). We discuss which physiological indicators are most informative for early detection and options for extending this capability to limited datasets such as those available from wearable, non-invasive, ECG-based sensors.

physiology↗

bioRxiv2017

A Single Mechanosensitive Channel Protects Francisella tularensis subsp. holarctica from Hypoosmotic Shock and Promotes Survival in the Aquatic Environment.

Francisella tularensis subspecies holarctica is found throughout the northern hemisphere and causes the disease tularemia in humans and animals. An aquatic cycle has been described for this subspecies, which has caused water-borne outbreaks of tularemia in at least 10 countries. In this study, we sought to identify mechanosensitive channel(s) required for the bacterium to survive the transition from mammalian hosts to freshwater, which is likely essential for transmission of the bacterium between susceptible hosts. A single mechanosensitive channel MscS (FTL_1753), among the smallest members of the mechanosensitive channel superfamily, was found to protect subsp. holarctia from hypoosmotic shock. Deletion of this channel did not affect virulence within the mammalian host, however mscS was required to survive the transition from the host niche to fresh water. Deletion of mscS did not alter the sensitivity of F. tularensis subspecies holarctica to detergents, H2O2, or antibiotics, suggesting that the role of MscS is specific to protection from hypoosmotic shock. Interestingly, deletion of mscS also led to reduced average cell size without altering gross cell morphology. The small mechanosensitive channel identified and characterized in this study likely contributes to the transmission of tularemia between hosts by allowing the bacterium to survive the transition from mammalian hosts to fresh water.

microbiology↗