A deep learning genome-mining strategy for biosynthetic gene cluster prediction.

Natural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers reduced false positive rates in BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing machine-learning tools. We supplemented this with random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable putative BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a major addition to in-silico BGC identification.

Impacts of Rotational Grazing on Soil Carbon in Native Grass-Based Pastures in Southern Australia.

Rotational grazing management strategies have been promoted as a way to improve the sustainability of native grass-based pasture systems. From disturbance ecology theory, rotational grazing relative to continuous grazing can increase pasture productivity by allowing vegetation to recover after short intense grazing periods. This project sought to assess whether soil organic carbon (SOC) stocks would also increase with adoption of rotational grazing management. Twelve pairs of rotationally and continuously grazed paddocks were sampled across a rainfall gradient in South Australia. Pasture productivity approximated as the normalized difference vegetation index (NDVI) was on average no different between management categories, but when the data from all sites were aggregated as log response ratios (rotational/continuous) a significant positive trend of increasing NDVI under rotational grazing relative to continuous grazing was found (R2 = 0.52). Mean SOC stocks (0-30 cm) were 48.3 Mg C ha-1 with a range of 20-80 Mg C ha-1 across the study area with no differences between grazing management categories. SOC stocks were well correlated with rainfall and temperature (multiple linear regression R2 = 0.61). After removing the influence of climate on SOC stocks, the management variables, rest periods, stocking rate and grazing days, were found to be significantly correlated with SOC, explaining 22% of the variance in SOC, but there were still no clear differences in SOC stocks at paired sites. We suggest three reasons for the lack of SOC response. First, changes in plant productivity and turnover in low-medium rainfall regions due to changes in grazing management are small and slow, so we would only expect at best small incremental changes in SOC stocks. This is compounded by the inherent variability within and between paddocks making detection of a small real change difficult on short timescales. Lastly, the management data suggests that there is a gradation in implementation of rotational grazing and the use of two fixed categories (i.e. rotational v. continuous) may not be the most appropriate method of comparing diverse management styles.

Use of soluble fibrin antigen instead of D-dimer as fibrin-related marker may enhance the prognostic power of the ISTH overt DIC score.

The overt DIC score of the DIC subcommittee of the ISTH includes a fibrin-related marker (FRM) as indicator of intravascular fibrin formation. The type of marker to be used has not been specified, but D-dimer antigen, or fibrin degradation products are used by most investigators. Soluble fibrin complexes have been suggested as more specific indicators of acute intravascular fibrin formation. The aim of the present study was to compare the predictive value of the overt DIC score concerning clinical outcome in a surgical intensive care cohort, using either D-dimer antigen, or soluble fibrin antigen as FRM. The cutoff values for 2 and 3 score points for the FRM were assigned on the basis of the 25% and 75% quartiles of 1870 plasma samples obtained from 359 ICU patients during a period of 6 months. For 331 patients with complete diagnostic workup and day 1 blood samples, the Iatro SF as FRM component of the overt DIC score displayed the highest prognostic power concerning clinical outcome. The 28-day mortality of patients with overt DIC at day 1, using Iatro SF as FRM assay was 50.0%, whereas 28-day mortality of patients without overt DIC was 14.0% (p <0.0001). Using MDA D-dimer, and TINAquant D-dimer, 28-day mortality was between 35.5% and 39.3% in patients with overt DIC, and 15.5% to 15.6% in patients without overt DIC. Selection of the FRM as component of the DIC score has a small, but relevant impact on the prognostic performance of the overt DIC score. The present data on the distribution of values may provide a basis for the selection of appropriate cutoff points for assigning 2, and 3 points in the score.

Utility of activated partial thromboplastin time waveform analysis for identification of sepsis and overt disseminated intravascular coagulation in patients admitted to a surgical intensive care unit.

OBJECTIVE: An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described in association with overt disseminated intravascular coagulation. This abnormality, a biphasic waveform, is caused by the in vitro formation of Ca2+-induced complexes between very low density lipoprotein and C-reactive protein. We have evaluated the diagnostic utility of aPTT waveform analysis for identifying patients with overt disseminated intravascular coagulation and sepsis. DESIGN: Observational study investigating the predictive value of biphasic waveform for the diagnosis of sepsis and overt disseminated intravascular coagulation. SETTING: Surgical intensive care unit of a university hospital. SUBJECTS: We studied 331 consecutive patients admitted to the intensive care unit during a period of 6 months. INTERVENTIONS: Laboratory analyses, including prothrombin time, aPTT, aPTT waveform analysis, fibrinogen, D-dimer antigen, and platelet count. MEASUREMENTS AND MAIN RESULTS: At the most sensitive threshold value of the waveform variable for detection of the biphasic waveform (slope_1 = -0.05 %T/sec), this abnormality was detected in 54 of 331 patients (16.3%) at admission and 95 of 331 patients (28.7%) during the entire course of intensive care unit treatment. At this threshold, 59.3% of patients with a biphasic waveform on admission and 45.3% with a biphasic waveform during the total intensive care unit course were diagnosed with sepsis. Depending on the threshold value of slope_1, the sensitivity of aPTT waveform analysis for detection of sepsis varied between 22% and 55% at admission and between 48% and 74% during the entire intensive care unit stay. The specificity for sepsis varied between 92% and 98% and between 81% and 94%, for admission and total intensive care unit course, respectively. Biphasic waveform showed a comparable specificity for the diagnosis of overt disseminated intravascular coagulation, albeit at a lower sensitivity. CONCLUSIONS: As an adjunct to routine coagulation testing in intensive care unit patients, aPTT waveform analysis is an elegant means for the rapid and highly specific identification of patients with sepsis.