TASK DEFINITION: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
PROBLEM: A common challenge in pathogen discovery by deep sequencing approaches is to recognize viral or subviral pathogens in samples of diseased tissue that share no significant homology with a known pathogen. Here we report a homology-independent approach for discovering viroids, a distinct class of free circular RNA subviral pathogens that encode no protein and are known to infect plants only. Our approach involves analyzing the sequences of the total small RNAs of the infected plants obtained by deep sequencing with a unique computational algorithm, progressive filtering of overlapping small RNAs (PFOR). Viroid infection triggers production of viroid-derived overlapping siRNAs that cover the entire genome with high densities. PFOR retains viroid-specific siRNAs for genome assembly by progressively eliminating nonoverlapping small RNAs and those that overlap but cannot be assembled into a direct repeat RNA, which is synthesized from circular or multimeric repeated-sequence templates during viroid replication. We show that viroids from the two known families are readily identified and their full-length sequences assembled by PFOR from small RNAs sequenced from infected plants. PFOR analysis of a grapevine library further identified a viroid-like circular RNA 375 nt long that shared no significant sequence homology with known molecules and encoded active hammerhead ribozymes in RNAs of both plus and minus polarities, which presumably self-cleave to release monomer from multimeric replicative intermediates. A potential application of the homology-independent approach for viroid discovery in plant and animal species where RNA replication triggers the biogenesis of siRNAs is discussed.

SOLUTION: Which are the smallest known subviral pathogens of plants?

PROBLEM: In cancer research, background models for mutation rates have been extensively calibrated in coding regions, leading to the identification of many driver genes, recurrently mutated more than expected. Noncoding regions are also associated with disease; however, background models for them have not been investigated in as much detail. This is partially due to limited noncoding functional annotation. Also, great mutation heterogeneity and potential correlations between neighboring sites give rise to substantial overdispersion in mutation count, resulting in problematic background rate estimation. Here, we address these issues with a new computational framework called LARVA. It integrates variants with a comprehensive set of noncoding functional elements, modeling the mutation counts of the elements with a -binomial distribution to handle overdispersion. LARVA, moreover, uses regional genomic features such as replication timing to better estimate local mutation rates and mutational hotspots. We demonstrate LARVA's effectiveness on 760 whole-genome tumor sequences, showing that it identifies well-known noncoding drivers, such as mutations in the TERT promoter. Furthermore, LARVA highlights several novel highly mutated regulatory sites that could potentially be noncoding drivers. We make LARVA available as a software tool and release our highly mutated annotations as an online resource (larva.gersteinlab.org).

SOLUTION: Which tool is used for the identification of recurrent variants in noncoding regions?

PROBLEM: In 1740, the Mon of Lower Burma revolted against the Toungoo Dynasty and founded the Restored Hanthawaddy Kingdom based in Pegu . Throughout the 1740s, the Hanthawaddy forces were winning against Upper Burma-based Toungoo armies. The Siamese were concerned by another rising power in Burma since a strong Burma historically meant future invasions to Siam. Concerned, the Siamese court readily gave protection to the Burmese governors of Martaban and Tavoy who had fled to Siam. In 1745, they sent a diplomatic mission to Ava to evaluate the political situation there, and were received by the Burmese king Mahadhammaraza Dipadi. They saw an Ava court that was on its last legs. By 1751, Restored Hanthawaddy forces were closing in on Ava. The Siamese concerns about the emergence of another strong dynasty based in Pegu appeared imminent. Perhaps as a precautionary measure, the Siamese decided to move their forward base into the upper coast in 1751. While it remains unclear as to whether the Siamese ever intended to go beyond the coast into mainland Lower Burma, the Siamese action nonetheless rang alarm bells in Pegu. Deeply concerned, the Hanthawaddy leadership withdrew two-thirds of their army back down to Lower Burma immediately after they had toppled the last Toungoo king in April 1752. This redeployment of Hanthawaddy troops proved a critical turning point in Burmese history as it gave nascent Upper Burmese resistance groups much needed breathing room. The Hanthawaddy command left less than 10,000 men to pacify all of Upper Burma. Taking advantage of light Hanthawaddy troops, one resistance group, the Konbaung Dynasty led by Alaungpaya, drove out Hanthawaddy troops from Upper Burma by May 1754. Konbaung armies invaded Lower Burma in 1755, and captured Pegu in 1757, ending the 17-year-old Mon kingdom.

SOLUTION:
Who sent a diplomatic mission to Ava in 1745?