Sensitivity of the Burrows-Wheeler Transform to small modifications, and other problems on string compressors in Bioinformatics

Extensive amount of data is produced in textual form nowadays, especially in bioinformatics. Several algorithms exist to store and process this data efficiently in compressed space. In this thesis, we focus on both combinatorial and practical aspects of two of the most widely used algorithms for compressing text in bioinformatics: the Burrows-Wheeler Transform (BWT) and Lempel-Ziv compression (LZ77). In the first part, we focus on combinatorial aspects of the BWT. Given a word v, r = r(v) denotes the number of maximal equal-letter runs in BWT(v). First, we investigate the relationship between r of a word and r of its reverse. We prove that there exist words for which these two values differ by a logarithmic factor in the length of the word. In other words, although the repetitiveness in the two words is preserved, the number of runs can change by a non-constant factor. This suggests that the number of runs may not be an ideal repetitiveness measure. The second combinatorial aspect we are interested in is how small alterations in a word may affect its BWT in a relevant way. We prove that the number of runs of the BWT of a word can change (increase or decrease) by up to a logarithmic factor in the length of the word by just adding, removing, or substituting a single character. We then consider the special character $used in real-life applications to mark the end of a word. We investigate the impact of this character on words with respect to the BWT. We characterize positions in a word where$ can be inserted in order to turn it into the BWT of a $-terminated word over the same alphabet. We show that, whether and where$ is allowed, depends entirely on the structure of a specific permutation of the indices of the word, which is called the standard permutation of the word. The final part of this thesis treats more applied aspects of text compressors. In bioinformatics, BWT-based compressed data structures are widely used for pattern matching. We give an algorithm based on the BWT to find Maximal Unique Matches (MUMs) of a pattern with respect to a reference text in compressed space, extending an existing tool called PHONI [Boucher et. al, DCC 2021]. Finally, we study some aspects of the Lempel-Ziv 77 (LZ77) factorization of a word. Modeling DNA short reads, we provide a bound on the compression size of the concatenation of regular samples of a word

When a Dollar Makes a BWT

TheBurrows-Wheeler-Transform(BWT)isareversiblestring transformation which plays a central role in text compression and is fun- damental in many modern bioinformatics applications. The BWT is a permutation of the characters, which is in general better compressible and allows to answer several different query types more efficiently than the original string. It is easy to see that not every string is a BWT image, and exact charac- terizations of BWT images are known. We investigate a related combi- natorial question. In many applications, a sentinel character $is added to mark the end of the string, and thus the BWT of a string ending with$ contains exactly one $character. We ask, given a string w, in which positions, if any, can the$-character be inserted to turn w into the BWT image of a word ending with the sentinel character. We show that this depends only on the standard permutation of w and give a combinatorial characterization of such positions via this permutation. We then develop an O(n log n)-time algorithm for identifying all such positions, improving on the naive quadratic time algorithm

On Compressing Collections of Substring Samples

Publisher Copyright: © 2022 Copyright for this paper by its authors. Use permitted under Creative Commons License Attribution 4.0 International (CC BY 4.0).Given a string X = X[1..n] of length n, and integers m and s, such that n > m ≥ 2s > 0, we consider the problem of compressing the string S formed by concatenating the substrings of X of length m starting at positions i ≡ 1 (mod s). In particular, we provide an upper bound of (2n − m)/s + 2z + (m − s) on the size of the Lempel-Ziv (LZ77) parsing of S, where z is the size of the parsing of X. We also show that a related bound holds regardless of the order in which the substrings are concatenated in the formation of S. If X is viewed as a genome sequence, the above substring sampling process corresponds to an idealized model of short read DNA sequencing.Peer reviewe

Education in anesthesia: three years of online logbook implementation in an Italian school

BACKGROUND: The progress of physicians through residency training in anesthesiology can be monitored using an online logbook. The aim of this investigation was to establish how residents record clinical activities in their computerized web-based logbooks during their first years of anesthesiology training. METHODS: For this retrospective observational trial, the ESSE 3(©) digital registry of the University of Modena and Reggio Emilia, Italy was used to record all anesthesia-related activities performed by three consecutive year-groups of residents (Groups A, B and C) between 2009 and 2012. The ratio of activities to sessions was chosen as a surrogate measure of compliance. RESULTS: A total of 41,348 actions were analyzed. The ratio of activities to sessions showed a statistically significant decline for all activities concerning the perioperative management of anesthesia, with a steady reduction from the first to the last year-group (Group A 23.7, Group B 14.1 and Group C 2.2; p = 0.003). CONCLUSIONS: An online activities logbook is a useful tool for recording and assessing the clinical activities undertaken by each resident during residency training in anesthesiology

L’Arte dell’osservazione, dall’opera artistica alla diagnosi Le prime esperienze in Sapienza Università di Roma, a Medicina e Chirurgia

This study describes how Visual Thinking Strategies (VTS) as a methodological practice can help medical students learn and acquire analytical ability. This ability, capable of improving observational acumen and generally acquired only after years of clinical experience, may be achieved also by recourse to the systematic and reasoned examination of the visual arts, in particular paintings. Students attending the third year Medicine and Surgery degree-course, within the ambit of the faculty’s integrated medical-scientific and humanities teaching-learning activities, followed an elective course which began with a preparatory-explanatory lecture on the analytical methodologies applied to the study of art, followed by a practical workshop held at Rome’s Galleria Borghese and ended with a third and final lecture where the students themselves provided the teachers who conducted the course with direct feedback regarding the three phases of the course. The students’ appraisal of the experiences was positive; the experiment is on-going and has been extended to embrace other courses held by the Sapienza University. Further observations are needed at present to validate the effectiveness to medical training of this kind of course in the long term, even though the limited number of experiments carried out in other countries, whose historical and artistic heritages are undoubtedly not so rich as Italy’s, attest to their undeniable usefulness to students of medicine and surgery at both analytical and, no less important, humanistic-educational level

Social Cognition Individualized Activities Lab for Social Cognition Training and Narrative Enhancement in Patients With Schizophrenia: A Randomized Controlled Study to Assess Efficacy and Generalization to Real-Life Functioning (Prot. n°: NCT05130853)

Subjects affected by schizophrenia present significant deficits in various aspects of social cognition, such as emotion processing, social perception and theory of mind (ToM). These deficits have a greater impact than symptoms on occupational and social functioning. Therefore, social cognition represents an important therapeutic target in people with schizophrenia. Recent meta-analyses showed that social cognition training (SCT) is effective in improving social cognition in subjects with schizophrenia; however, real-life functioning is not always ameliorated. Integration of SCT with an intervention targeting metacognitive abilities might improve the integration of social cognitive skills to daily life functioning. Our research group has implemented a new individualized rehabilitation program: the Social Cognition Individualized Activities Lab, SoCIAL, which integrates SCT with a module for narrative enhancement, an intervention targeting metacognitive abilities. The present multi-center randomized controlled study will compare the efficacy of SoCIAL and treatment as usual (TAU) in subjects diagnosed with a schizophrenia-spectrum disorder. The primary outcome will be the improvement of social cognition and real-life functioning; while the secondary outcome will be the improvement of symptoms, functional capacity and neurocognition. The results of this study will add empirical evidence to the benefits and feasibility of SCT and narrative enhancement in people with schizophrenia-spectrum disorders

Altered bone development and turnover in transgenic mice over-expressing lipocalin-2 in bone

Lipocalin-2 (LCN2) is a protein largely expressed in many tissues, associated with different biological phenomena such as cellular differentiation, inflammation and cancer acting as a survival/apoptotic signal. We found that LCN2 was expressed during osteoblast differentiation and we generated transgenic (Tg) mice over-expressing LCN2 in bone. Tg mice were smaller and presented bone microarchitectural changes in both endochondral and intramembranous bones. In particular, Tg bones displayed a thinner layer of cortical bone and a decreased trabecular number. Osteoblast bone matrix deposition was reduced and osteoblast differentiation was slowed-down. Differences were also observed in the growth plate of young transgenic mice where chondrocyte displayed a more immature phenotype and a lower proliferation rate. In bone marrow cell cultures from transgenic mice, the number of osteoclast progenitors was increased whereas in vivo it was increased the number of mature osteoclasts expressing tartrate-resistant acid phosphatase (TRAP). Finally, while osteoprotegerin (OPG) levels remained unchanged, the expression of the conventional receptor activator of nuclear factor-κB ligand (RANKL) and of the IL-6 was enhanced in Tg mice. In conclusion, we found that LCN2 plays a role in bone development and turnover having both a negative effect on bone formation, by affecting growth plate development and interfering with osteoblast differentiation, and a positive effect on bone resorption by enhancing osteoclast compartment

Evaluation of DNA Methylation Profiles of LINE-1, Alu and Ribosomal DNA Repeats in Human Cell Lines Exposed to Radiofrequency Radiation

A large body of evidence indicates that environmental agents can induce alterations in DNA methylation (DNAm) profiles. Radiofrequency electromagnetic fields (RF-EMFs) are radiations emitted by everyday devices, which have been classified as "possibly carcinogenic"; however, their biological effects are unclear. As aberrant DNAm of genomic repetitive elements (REs) may promote genomic instability, here, we sought to determine whether exposure to RF-EMFs could affect DNAm of different classes of REs, such as long interspersed nuclear elements-1 (LINE-1), Alu short interspersed nuclear elements and ribosomal repeats. To this purpose, we analysed DNAm profiles of cervical cancer and neuroblastoma cell lines (HeLa, BE(2)C and SH-SY5Y) exposed to 900 MHz GSM-modulated RF-EMF through an Illumina-based targeted deep bisulfite sequencing approach. Our findings showed that radiofrequency exposure did not affect the DNAm of Alu elements in any of the cell lines analysed. Conversely, it influenced DNAm of LINE-1 and ribosomal repeats in terms of both average profiles and organisation of methylated and unmethylated CpG sites, in different ways in each of the three cell lines studied