integrated phd entrance exam 2022

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IISER Tirupati

The BS-MS curriculum is organized around a credits based semester system with two semesters in each academic year. The emphasis is on concept based and enquiry driven education integrating teaching with research in an interdisciplinary manner . The BS-MS program offers basic courses in all Sciences for the first four semesters I-IV of the program. This is followed by advanced courses at MS level, in semesters V-VIII where students have the option to choose their courses based on their intertest and inclination. In the final year, students do a research project leading to MS thesis. 

Integrated PhD

IISER Tirupati invites applications from prospective candidates for admission to the PhD programme, August 2022. IISER Tirupati admits students in the disciplines of Biology, Chemistry, Physics, Mathematics, Earth and Climate Sciences and associated interdisciplinary areas of research. In addition to research, the programme involves coursework and teaching assistantship.

The department-specific eligibility criteria for August 2022 admissions are given below. Information about individual faculty profiles and areas of research can be obtained from the IISER Tirupati website.

In this round, the departments of Biology, Chemistry, Physics, Mathematics and Earth and Climate Sciences will admit PhD students.

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PhD / Integrated Phd - Admissions - 2022

Admission to PhD ./ Integrated PhD programmes are open.

• Ph D / Integrated Ph D -- Selection List

Shortlisted candidates for the Interview

Selected candidates for JRF PhD Programme in Computational Biology

Theoretical Computer Science - JEST 2022 - Shortlisted for Interview

Integrated Ph. D Programmes

INTEGRATED Ph.D. PROGRAMME

Eligibility :

Selection procedure :

Shortlisting for interviews for selection to the Int. Ph.D. Physical Science programme will be based on academic records, performance in the national level exams, statement of purpose mentioned in the application form.

Shortlisting for interviews for Int. Ph.D. Chemical Science programme will be done based on the performance in Joint Admission test for Master’s (JAM) 2024 or a written examination conducted by JNCASR.

The applications for the Int. Ph.D. Biological Science programme will be screened based on overall academic performance for eligibility to attend an entrance exam. Successful candidates will be invited to appear for interviews shortly afterwards.

The final selection to the Int. Ph.D. Degree Programme will be based on the performance in the interview.

Note: Interviews will be held in-person only .

Scholarships/Fellowships: Integrated Ph.D. students are paid fellowship of Rs.19000/- for first two years, Rs.37,000/- during third and fourth year and Rs.42,000/- during fifth, sixth and seventh year.

Medical / Insurance facility: Students are automatically enrolled in a Group Insurance Scheme and a Comprehensive Medical Scheme and have access to an on-campus doctor, as well as to medical facilities elsewhere.

Travel grants:  While pursuing Ph.D. from third year onwards, one time  students travel grant upto Rs.1,00,000/- is provided to attend international/national conferences.

Our students have attended conferences in countries such as Korea, Iran, France, Singapore, the United States of America, Japan, Sweden, Italy, Israel, etc.

Tuition Fee, etc :  Current norms for payment of tuition fees is Rs.5,000/- per annum for first two years and Rs.10,000/- per annum for the next five years. In addition, Rs 200 as medical charges and group insurance fee of Rs. 25 will be charged every month.

Link to degree programme

© 2021, JNCASR, Jakkur, Bangalore, India

Department of Mathematical Sciences

Indian Institute of Science Education And Research, Mohali

Announcement for Integrated PhD Admissions

The following email was sent to all applicants on 22nd June 2022. Please check your spam if you have not received it. Do contact us in case of any discrepancy.

Dear Student, Thank you for applying to the Integrated PhD programme in Mathematics at IISER Mohali. In this regard, you are requested to be present on the 18th of July at IISER Mohali for a screening test and (if you clear the test) for an interview. Only candidates who clear the screening test will be interviewed. Here are the details: DATE: 18th of July, 2022 (Monday) REPORTING TIME: 7:30 AM SCREENING TEST: 8:00 AM to 10:00 AM INTERVIEWS: 12:00 PM onward IMPORTANT: Interviews may last till 7:30 PM so please plan your travel accordingly. You are requested to acknowledge this email and confirm that you will attend the interview, within 10 days by replying to this email with a copy to  [email protected] DOCUMENTS TO BE PRODUCED AT THE TIME OF THE INTERVIEW: Applicants must bring with them a printout of this email invitation for the interview, a passport size photograph, and original versions and self attested photocopies of all relevant certificates (e.g. marksheet, proof of clearing any national level qualifying examination, etc.) to support the information provided in the application form. DETAILS REGARDING ADMISSION: The results will be announced on the IISER Mohali website ( www.iisermohali.ac.in ). Successful candidates will also be informed individually of their admission. The offer of admission will be withdrawn if the selected candidate does not meet the eligibility criteria at the time of admission, or if any information provided in the application form is found to be false. SOME GENERAL INFORMATION: Applicants must be prepared to be available at IISER Mohali from 7:30 AM to 7:30 PM on the 18th of July, 2022 for the screening test and interview. IISER Mohali will NOT be able to provide any accommodation or reimburse expenses for it. The institute does NOT reimburse your travel expenses for appearing for the written test and/or interview for admission to the Integrated PhD program. You are requested to make your own arrangements for travel and accommodation. If you have any questions, please write to,  [email protected] Yours sincerely, Shane D’Mello Convenor, Integrated Ph.D. admissions, 2022 From: [email protected]

S. N. Bose National Centre for Basic Sciences

Under department of science and technology, govt. of india.

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Result of the Interview for the Admission 2022-23

Admission 2022-23: integrated ph.d. programme.

Dates of Interview: 30th May & 31st May 2022

The following students are selected for admission in the Integrated Ph.D. Programme for the Academic Year 2022-23:

1 st List of Selected Candidates (in alphabetical order of names)

[Candidates willing to join the programme need to confirm their acceptance by 15th June, 2022 at [email protected] or in person at the office of the Deputy Registrar (Academic) (Room: 218). They are also required to submit a Surety Deposit of Rs. 7000/- by Bank Transfer ( Click here for details ) or by Demand Draft drawn in favour of "S N Bose National Centre for Basic Sciences", payable at "Kolkata". Surety Deposit is refundable only after successful completion of the programme.]

Sd/- Dean(Academic Programme)

Wait Listed Candidates

(will be operative, if necessary, after 15 th June 2022)

Manipal Centre for Natural Sciences

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Integrated Ph. D

This Integrated Ph.D. program is open for students with Bachelor’s degree , highly meritorious, and motivated towards fundamental research in Natural Sciences such as physics, chemistry, earth and planetary sciences, evolutionary and developmental biology. However, for the current academic year, only Physics discipline is available, with a choice of specialization in (i) Astrophysics, (ii) Nuclear Physics. A student in this program, would complete the courses mandatory for a Ph.D., along with the courses essential for an MSc., during the first two semesters, and also acquire ample research experience by working on a research project, during the 3 rd and the 4 th semesters. Ph.D. level work begins at the 5 th semester. Such a student would be more equipped, than a regular MSc student, while beginning to do Ph.D. level work. 

The focus would be to bring out the research skills of a motivated Bachelor student. Added courses and projects, at Master’s and Ph.D. levels, would aim at building the student’s strength in the concept, and in the experimental, analytical, modeling and computational skills, towards understanding a complex natural phenomenon, even while pursuing studies for the Ph.D. degree, on a frontier problem in the chosen discipline.

Career Prospects:

Since the emphasis is on high quality research work, a student obtaining Ph.D. degree under this program would have acquired remarkable skills in research, from approach to the problem to its solution, and hence would have a competitive edge while seeking an academic position or employment as a professional researcher in a reputed institution in India or abroad.

5.5 Years (including M.Sc.)

Academic Calender

Calender :   INTEGRATED PHD PROGRAMME in PHYSICS

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BITS Pilani is a Deemed to be University, offering on-campus programs to more than 18,500 students across its campuses in Pilani, Goa, Hyderabad, Mumbai and Dubai.It has been recognized as an Institute of Eminence by the Ministry of Education, Government of India in 2020.

QS World University Subject Rankings 2024 has ranked BITS Pilani globally at

• 101-150 in Pharmacy and Pharmacology
• 301-350 in 4 subjects namely, EEE, Computer Science, Mechanical and Chemical Engineering
• 451-500 in 3 subjects, namely, Mathematics, Business & management Studies and Physics & Astronomy
• 501-550 in Chemistry

In ǪS Asia University Rankings 2024, BITS has been ranked 215th in Asia and at 22nd in India. Further, BITS Pilani has been ranked among the top 300 in ǪS World University Graduate Employability Rankings 2022 and within top 6 in India.

Having pioneered several curricular and pedagogic attributes, BITS Pilani has a vision to be amongst the top research-led Institutes in the country. The qualities of innovation, enterprise, commitment to excellence, adherence to merit, and transparency, have characterized the Institute during its inexorable march to eminence.

The Institute has secured over Rs 398 crores as external research funding in the last 5 years. State of the art facilities have been developed to support cutting edge research, led by students and about 930 faculty members, leading to a Scopus h-index of 156, with 221 patents filed so far, and 41 patents granted. Currently, there are 14 BITSian Unicorns and 1 Decacorn. There are over 7500 BITSian founders and co-founders of enterprises.

Doctoral Programme (Ph.D.)

List of Candidates shortlisted for Ph.D. Admission Test and/or Interview is now available

Admissions portal open 01st march 2024.

Please click here for more information.

List of Candidates shortlisted for Ph.D. Admission Test and/or Interview is now available.

• CLICK HERE to know the Result.

Department preference with regard to the full-time and part-time Ph.D student admission is given in the table below.

Yes – A Department intends to admit students under the specified mode. No – A Department does not intend to admit students under the specified mode.

Minimum Eligibility Qualifications

ME / MTech / MPharm / MBA / MPhil (minimum of 60% aggregate)* MSc/BE/BPharm or an equivalent degree (minimum of 60% aggregate)* For admission into Humanities and Social Sciences, MA degree (minimum of 55% aggregate)* For part-time applicants, a minimum of one-year experience in the related field of study is required

[*In the Qualifying Degree examination]

In addition, Departments may set specific admission criteria for shortlisting. Meeting the minimum eligibility qualifications does not guarantee admission into the PhD program. Shortlisted candidates will have to appear for an admission test, which may comprise a written exam and/or interview. Information on specific Departments and related research activities is available on the Department homepage of respective campuses.

Full-time students

Preferably individuals who would like to pursue PhD in-house, residing on campus.

Part-time students

Preferably individuals who are working in organizations providing basic facilities and an environment for research.

Financial Assistance

Full-time PhD students admitted into the PhD program are eligible to be considered for an Institute fellowship of Rs. 34,000 or Rs. 37,000 per month in the first year based on their qualifications at the time of admission. Students admitted with M.E./M.Tech./M.Pharm./MBA/M.Phil. or an equivalent Degree are eligible to receive an Institute fellowship of Rs. 37,000/-. Students admitted with M.Sc./B.E./B.Pharm. or an equivalent degree are eligible to receive an Institute fellowship of Rs. 34,000/-. These students on successful completion of coursework will receive Rs. 37,000/- from the Semester following the one in which the course work was completed Higher fellowship may be made available in subsequent years. Consideration for Institute fellowship will be as per Institute norms. It will be obligatory on the part of every admitted full time student to undertake 8 hours (per week) of work as assigned to him/her by the institute.

Important Dates

The Institute reserves the right to change the above deadlines. Candidates will be informed in advance should there be such a change.

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Pilani campus – biological sciences, pilani campus – chemistry, pilani campus – chemical engineering, pilani campus – civil engineering, pilani campus – electrical & electronics engineering, pilani campus – humanities and social sciences, pilani campus – physics, pilani campus – mechanical engineering, goa campus – biological sciences, goa campus – chemistry, goa campus – computer sciences, goa campus – electrical & electronics engineering, goa campus – humanities and social sciences, goa campus – mathematics, goa campus – mechanical engineering, hyderabad campus – biological sciences, hyderabad campus – chemical engineering, hyderabad campus – chemistry, hyderabad campus – civil engineering, hyderabad campus – computer sciences, hyderabad campus – electrical & electronics engineering, hyderabad campus – humanities and social sciences, hyderabad campus – mathematics, hyderabad campus – mechanical engineering, hyderabad campus – pharmacy, top resources.

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Birla Institute of Technology & Science, Pilani Campus, Pilani, Rajasthan 333031 (INDIA).

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Integrated MS-PhD in Biotechnology with specialization in Biomedical Genomics

NIBMG has been running its Integrated MS-PhD program since 2019. Students admitted into the program undergo master’s coursework during the first two years. This includes Master’s projects carried out in a research lab(s) under the mentorship of NIBMG faculty, during the third and fourth semesters.

After the first 2 years, based on the overall performance and eligibility criteria of the institute, a student may be permitted to continue in the programme for pursuing PhD thesis research. Students unable to qualify for continuing in the PhD component will be asked to exit the program with an MS degree. After switching over to PhD component, PhD thesis should be submitted not earlier than 3 years and not later than 5 years.

Curriculum:

Integrated MS-Ph.D. program has a blend of theoretical courses, practical (hands-on) lab courses, and projects in research laboratories. The first semester courses focus on basic biology such as Biochemistry, Cell Biology, Molecular Biology, Immunology, Principles of Genetics etc. Second semester introduces Human Genetics and Genomics, Biostatistics, Data Analysis (in R) and includes courses related with genetic aspects of human diseases such as cancer, infectious and chronic diseases. Along with the lectures and practical, each student undergoes research lab rotation in the major research areas: (Cancer, Infectious disease, Chronic disease and Computational Biology and Statistical Genomics) during first two semesters. The Third semester includes a few courses on Research Methods, Scientific Communication, advanced genomics/ bioinformatics courses in addition to research project under the assigned supervisor. The 4th semester students will only undertake project work, that has been initiated.

Research at NIBMG:

Research activities at NIBMG are centred around the common theme of understanding genomic background of human health and disease. NIBMG is equipped with state-of-the-art technologies which include single-cell sequencing and Next Generation Sequencing platforms, robotics platforms, high-end computational and bioinformatics facility, cell and molecular biology facilities, genetic engineering including cutting-edge CRISPR-Cas Genome editing laboratories, FACS (cell sorter), low and high- resolution imaging facility, BSL3 facility, bacteriology and radioactivity labs, state-of-the-art zebrafish, proteomics, metabolomics and microbiome facilities.

The broad areas of research pursued at NIBMG are:

1) Biomedical Genomics and the functional implications in the context of: A. Cancer B. Infectious disease C. Chronic disease

2) Computational Biology and Statistical Genomics

Minimum Eligibility:

Indian nationals with minimum 55 % aggregate marks (or an equivalent grade point average) in bachelor’s degree in any branch of Biological Sciences are eligible to apply. Students from the SC, ST, OBC (non-creamy layer), and PwD categories shall be given a relaxation of 5% marks. Students in the last year of their bachelor’s degree are also eligible to apply, provided they can produce a proof of having secured the minimum aggregate marks at the time of admission.

Candidates who fulfil the minimum eligibility conditions and have qualified any of the following entrance exams (in the current year or latest exam held) may apply online.

1) Joint Graduate Entrance Examination for Biology and Interdisciplinary Life Sciences (JGEEBILS conducted by NCBS/TIFR)

2) Joint Admission Test for M.Sc. JAM- in Biotechnology (BT).

Selection procedure:

Candidates will be shortlisted for interview if their scores in JGEEBILS or JAM (BT) are higher than the cut-offs determined by NIBMG. Short listed candidate will be called for interview for final selection. Final selection is based exclusively on the candidate’s Interview performance. There shall be reservation of seats for students from the SC, ST, OBC, PwD and EWS categories as per the orders of the Govt. of India in this regard.

Continuation in PhD:

After the first 2 years, based on the overall performance and eligibility criteria of the institute, a student may be permitted to continue in the programme for pursuing PhD thesis research. Students unable to qualify for switching over to PhD component will be asked to exit the program with an MS degree. After the first two years of the program, a student can also exercise his/her choice to exit the programme with an MS degree. In either case, students exiting the program shall be eligible for the MS degree only after fulfilling course requirements, minimum CGPA and satisfying all other Institute requirements as stipulated by the competent authority. 

Fellowships:

The students admitted to the program receive a fellowship of Rs. 16,000/- per month while pursuing the MS part. After the first 2 years, those who are permitted to continue in the PhD component of the program but have not qualified any national level fellowships (e.g., NET JRF) will be provided PhD fellowship as per approved norms.

Hostel Facilities:

On campus accommodation facility is available for all admitted students on payment of prescribed fees; it is mandatory for all students to stay in the Hostel during the entire course of study. For details regarding the amenities available at NIBMG hostel please visit https://www.nibmg.ac.in/p/amenities-in-hostel . A canteen facility is available on campus where food is served against monthly subscription paid in advance.

* Fees are subject to change from time to time as stipulated by competent authority.

Contact Details:

More From Forbes

Legacy admission preferences linked to college inequities finds report.

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A new report highlights the student differences at colleges that extend a legacy admissions ... [+] preference versus those that don't.

Colleges and universities that give an admission preference to applicants who are related to alumni enroll lower proportions of Black, Hispanic and low-income students than those institutions who don’t extend a so-called legacy preference.

That’s a main conclusion from a new report by the Institute for Higher Education Policy, which analyzed enrollment data for academic years 2021–22 and 2022–23 released through the Integrated Postsecondary Education Data System (IPEDS).

Legacy Admissions Policies Remain Common

Even though more than 100 institutions have eliminated legacy admission policies since 2015, and three states (Colorado, Virginia and Maryland) have now banned the practice, it continues to be prevalent especially at institutions that apply more selective admission policies.

Almost one third (32%) of all selective four-year higher education institutions in the U.S. considered the legacy status of applicants during the 2021-2022 academic year. These policies were particularly common at selective private nonprofit four-year institutions, where 42% considered applicants’ legacy status. But even at selective public four-year colleges, 15% considered an applicant’s alumni ties to the institution when making admissions decisions.

In the 2021-2022 academic year, 2.1 million undergraduate students enrolled in institutions considering legacy status in their admissions decisions. Public four-year colleges accounted for nearly 40% of those students.

Best High-Yield Savings Accounts Of 2024

Best 5% interest savings accounts of 2024, legacy preferences and student enrollment differences.

Selective institutions that don’t consider legacy status in their admission decisions are more racially diverse, with higher proportions of Black and Hispanic students compared to selective institutions that do consider legacy status in admissions.

At selective institutions that take legacy relationships into account, 59% of undergraduates are white, compared to 51% at those institutions that don’t consider legacy status. A lower percentage of Hispanic students (12%) were enrolled at schools with legacy preferences compared to those not using such a policy (15%). A similar pattern was found for Black students, who comprised 11% of undergraduates at institutions with a legacy preference compared to 14% at those without such a policy.

Selective four-year institutions that do not consider legacy status also have a larger proportion of students from low-income backgrounds. Forty-two percent of full-time, first-time undergraduates at these institutions receive Pell Grants, compared to 36% at selective four-year institutions that do consider legacy in admissions. And as the report notes, “students who are the first in their families to attend college are particularly disadvantaged by legacy admissions policies because their parents have not earned a degree.”

The report concluded, “when colleges consider legacy in their admissions process, they prioritize access for children of college-educated families who are disproportionately white and well-off..., tilting the scales against Black and Hispanic students and students from low-income backgrounds.”

There’s been slow but steady progress in ending legacy preferences in college admissions. Its fairness has been challenged for years, but the heat has been turned up against the practice ever since last year’s Supreme Court decision in Students for Fair Admissions v. Harvard University and Students for Fair Admissions v. University of North Carolina finding race-conscious admissions to be unconstitutional.

That ruling highlighted what many observers regard as an obvious double standard – prohibiting policies that give an edge to underrepresented minority students while at the same time permitting legacy preferences that primarily benefit white students who tend to come from affluent backgrounds.

New organizations, such as Class Action , a national effort by college students to work for more equitable admission practices at elite colleges, are bringing more pressure to end policies that consistently favor the wealthy and discriminates against the poor. But as this report documents, legacy preferences are still widespread and they continue to limit student access to college.

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• Open access
• Published: 08 July 2024

Integrated proteomic and metabolomic profiling reveals novel insights on the inflammation and immune response in HFpEF

• Muyashaer Abudurexiti 1 ,
• Refukaiti Abuduhalike 1 ,
• Tuersunjiang Naman 1 ,
• Nuerdun Wupuer 1 ,
• Dongqin Duan 1 ,
• Mayire Keranmu 1 &
• Ailiman Mahemuti 1  

BMC Genomics volume  25 , Article number:  676 ( 2024 ) Cite this article

Metrics details

The precise mechanisms leading to the development of heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. In this study, an integrative approach utilizing untargeted proteomics and metabolomics was employed to delineate the altered proteomic and metabolomic profiles in patients with HFpEF compared to healthy controls.

Materials and methods

Data were collected from a prospective cohort consisting of 30 HFpEF participants and 30 healthy controls, matched by gender and age. plasma samples were analyzed by multi-omics platforms. The quantification of plasma proteins and metabolites was performed using data-independent acquisition-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), respectively. Additionally, Proteomic and metabolomic results were analyzed separately and integrated using correlation and pathway analysis. This was followed by the execution of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment studies to elucidate the biological relevance of the observed results.

A total of 46 significantly differentially expressed proteins (DEPs) and 102 differentially expressed metabolites (DEMs) were identified. Then, GO and KEGG pathway enrichment analyses were performed by DEPs and DEMs. Integrated analysis of proteomics and metabolomics has revealed Tuberculosis and African trypanosomiasis pathways that are significantly enriched and the DEPs and DEMs enriched within them, are associated with inflammation and immune response.

Conclusions

Integrated proteomic and metabolomic analyses revealed distinct inflammatory and immune response pathways in HFpEF, highlighting novel therapeutic avenues.

Peer Review reports

Introduction

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure cases and is characterized by diastolic dysfunction and preserved left ventricular ejection fraction [ 1 , 2 ]. HFpEF is initiated by a variety of metabolic-altering factors such as hypertension, obesity, diabetes, and aging [ 3 ]. Despite its significant prevalence and substantial clinical impact, HFpEF continues to be a difficult condition to manage. This is attributed to the absence of universally effective therapeutic options and a comprehensive understanding of its underlying pathophysiology [ 4 , 5 ]. The pathophysiology of HFpEF involves a complex interplay between comorbidities that impose a systemic proinflammatory state, myocardial stiffness, impaired ventricular-arterial coupling, and microvascular endothelial inflammation [ 6 , 7 ]. however, the metabolic and molecular alterations that ultimately produce these changes are not well established [ 8 ].

Proteomics and metabolomics are ‘omics’ technologies that comprehensively analyze the entire proteome and metabolome within specific biological samples [ 9 ]. Unlike genetics, which focuses on the hereditary aspects of diseases, proteomics and metabolomics provide insights into the phenotype and progression of diseases [ 10 ]. Integrative analysis that combines proteomic and metabolomic profiling has been shown to provide novel insights into the understanding of disease mechanisms and their development [ 11 ]. These ‘omics’ technologies enable the comprehensive profiling of proteins and metabolites within biological samples, providing a snapshot of the physiological state and pathophysiological changes occurring in disease conditions [ 12 , 13 ].

This study analyzed date-independent acquisition (DIA)--based proteomics and high-resolution mass spectrometry metabolomics profiling of plasma samples from HFpEF patients and healthy control. We aim to quantify and identify differentially expressed proteins and metabolites that may contribute to the pathogenesis of HFpEF. The integration of proteomic and metabolomic data through correlation and pathway analysis, complemented by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, allows for a comprehensive examination of the dysregulated biological pathways in HFpEF. The following sections, we will detail the methodology of omics analyses, present the key findings, particular focus on inflammation and immune response, and discuss the potential implications of data for the clinical management and therapeutic targeting of HFpEF.

Patient recruitment and sample collection

With the approvement by the Ethics Committee of the First Affiliated Hospital of Xinjiang Medical University (IRB- K202403-12), Between March to July 2023, a cohort of 30 newly diagnosed HFpEF patients 30 healthy controls were consecutively assembled at the Heart Failure Department of the First Affiliated Hospital of Xinjiang Medical University. These individuals, newly diagnosed with HFpEF upon admission, before the initiation of any treatment, aged between 18 and 85, provided informed consent, and pertinent participant attributes are detailed in Table S1 . All participants had been diagnosed with HFpEF according to established consensus criteria [ 14 , 15 , 16 ]. The criteria for inclusion involved encompassed symptoms and signs of exertional dyspnea (New York Heart Association class II or III), heart failure with a left ventricular ejection fraction (LVEF) of ≥ 50%, and at least two of the following conditions: [ 1 ] elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels ≥ 125 pg/mL; [ 2 ] identification of structural heart abnormalities or diastolic dysfunction via echocardiography, and [ 3 ] E/e’ ratio ≥ 9. Excluded from participation were individuals with a medical history encompassing congenital heart defects, LVEF < 40%, heart failure categorized as mid-range EF (40–50%), hypertrophic cardiomyopathy, prior cardiac transplantation, constrictive pericarditis, severe valvular disorders, or infiltrative or restrictive cardiomyopathies. The control group was comprised of patients without overt HF characterized by LVEF ≥ 50% and NT-pro-BP concentrations < 125 ng/L.

Plasma samples were collected from patients who received a new diagnosis of HFpEF upon admission, following overnight fasting to minimize dietary influences. Blood was drawn into vacuum-sealed, EDTA-treated tubes to prevent coagulation. After centrifugation at 3000 rpm for 10 min, the supernatant was carefully collected and stored at -80 °C until further analysis.

Proteome analysis

Utilizing data-independent acquisition (DIA)-based proteomics, LC-MS/MS analysis was conducted to examine proteins in plasma. The proteins were introduced into a mass spectrometer (Q Exactiv HF-X; Thermo Fisher, Germany) linked to a chromatography platform (EASY-nL 1200 UHPLC system; Thermo Fisher, Germany) with DIA mode selected for data collection. Differentially expressed proteins (DEPs) of significant interest were identified based on a fold-change of ≥ 1.5 or ≤ 0.67 and a t-test p -value of < 0.05 [ 9 ]. Subsequent mapping of DEPs and pathway analysis was facilitated utilizing the KEGG pathway database. Detailed experimental protocol of proteomics was provided in the Supplementary material.

Metabolomics analysis

Untargeted metabolomic investigations were carried out using LC-MS/MS analysis. The Vanquish UHPLC system (ThermoFisher, Germany) was coupled with either an Orbitrap Q Exactive HF or an Orbitrap Q Exactive HF-X mass spectrometer (Thermo Fisher, Germany) for metabolite separation and identification. Differential expression of metabolites (DEMs) was assessed based on criteria including Variable Importance in Projection (VIP) > 1.0, Fold Change (FC) > 1.2 or FC < 0.833, and a significance level of P-value < 0.05 [ 9 ]. The metabolic pathways enriched in DEM were analyzed using the KEGG database. Detailed experimental protocol of metabolomics was provided in the Supplementary material.

Correlation analysis between proteomics and metabolomics

Pearson correlation analysis was utilized to investigate the relationships between DEPs and DEMs,

considering p-value  < 0.05 and correlation coefficient > 0. Subsequently, KEGG pathway enrichment analysis was conducted for the DEPs and DEMs.

Proteomic profiling analysis of HFpEF and HC samples

Altogether, 6026 peptides and 689 proteins were identified. The PLS-DA analysis used to detect differences among HFpEF patients and HC, indicate clear separations between the two groups (R2Y = 0.93, Q2 Y = 0.47, Fig.  1 A). The results of the permutation test strongly indicated that the original model was valid (R2 intercept = 0.91, Q2 intercept = − 0.35, Fig.  1 B), suggest that the PLS-DA model is not overfitting. The volcano plot revealed a distinct distribution of protein expression changes between the HFpEF and HC groups. We plotted fold changes (using volcano plots) in the levels of identified proteins in HFpEF patients relative to HC groups, A total of 46 proteins showed Significantly differentially expressed proteins (DEPs), among which 36 were significantly upregulated, and 10 were significant downregulated (Fig. 1C, Table S2 ). of these 21 were associated with inflammation and immune responses, all of that were upregulated in the HFpEF group compared with the HC group. The upregulation of these proteins, particularly IGHV3-64, IGKV2-40, IGLV2-18, and SAA1, suggests an altered immune response in HFpEF patients. The biological function of each DEP was identified through GO analysis and evaluated based on the KEGG. The GO enrichment analysis showed that these DEPs were mainly concentrated in response to stimulus in biological Processes (Fig.  1 D), extracellular region in Cellular Component (Fig.  1 E), and protein binding in Molecular Function (Fig.  1 F). In order to understand the functional characteristics and classification of these DEPs, we conducted pathway enrichment analysis using the KEGG and identified the significant enriched pathways. Based on the KEGG database, the main pathways involved PI3K − Akt signaling and Tuberculosis pathway (Fig.  1 G).

Metabolomic profiling analysis of HFpEF and HC samples

As shown in (Fig. S1 A, B), there are distinct clusters of metabolites in HFpEF patients compared with control individuals in both ESI + and ESI − . Subsequently, the reliability of the partial least-squares discriminant analysis (PLS-DA) model was assessed using a permutation test. The intercepts of goodness-of-fit (R2) and goodness-of-prediction (Q2) illustrate the PLS-DA model is reliable and not overfitting (Fig. S1 C, D). We plotted fold changes (using volcano plots) in the levels of identified metabolites in HFpEF patients relative to HC groups, Totally, 124 DEMs were discovered (Fig.  2 A, B). Of these,12 positive downregulated DEMs are phospholipids, which are critical components of all cell membranes and play a key role in lipid metabolism (Table S3 ). Then, we conducted pathway enrichment analysis using the KEGG and identified the significant enriched pathway in both ESI + and ESI − models. We found that Tryptophan metabolism, Tuberculosis, steroid biosynthesis, Endocrine, and other factor-regulated calcium reabsorption were the top pathways altered in DEMs (Fig.  2 C, D).

Integrated analyses of proteomics and metabolomics data correlation analysis

We conducted an integrated analysis of proteomics and metabolomics and found that there were 36 upregulated DEPs, 10 downregulated DEPs, 108 significantly upregulated metabolites, and 16 downregulated metabolites (Fig. S1 E); After our initial analysis, we proceeded with a hierarchical cluster analysis between the DEPs and DEMS to appraise protein-metabolites relationship in the HFpEF patients (Fig.  3 A). Consequently, a pronounced correlation was observed in the DEPs and DEMs. Integrative analysis via KEGG of the proteins and metabolites showing differential abundance revealed that the main pathways implicated included those associated with Tuberculosis and African trypanosomiasis (Fig.  2 B, C). Interestingly, we found that most of the DEPs enriched in this pathway are associated with Inflammation and Immune Response (Fig.  1 F, G, Table S4 ). We reviewed the patients’ history and found that none of the patients with HFpEF had Tuberculosis and African trypanosomiasis. Inflammation and Immune response are thought to play an important role in the pathogenesis of tuberculosis and African trypanosomiasis disease [ 17 , 18 ]. Therefore, the proteins that may be related to inflammation are enriched in “Tuberculosis and African trypanosomiasis” signaling pathways.

In recent times, proteomics and metabolomics have emerged as innovative tools not only for identifying new risk factors but also for elucidating the underlying mechanisms of cardiovascular disease [ 9 ]. Previous studies have revealed aberrant alterations in numerous proteins and metabolites among patients with HFpE [ 19 , 20 , 21 , 22 ]. For instance, Virginia S. Hahn and colleagues observed decreased levels of fatty acid metabolites in the myocardium of HFpEF patients compared to those with heart failure with reduced ejection fraction (HFrEF). Furthermore, reductions in ketones, metabolites of the tricarboxylic acid cycle, and branched-chain amino acids (BCAA) were noted in HFpEF, indicating a potential inadequacy in utilizing alternative energy sources [ 23 ]. Luigi Adamo suggested the feasibility of employing high-content multiplexed proteomics assays in conjunction with the clinical evaluation of LVEF to enhance the identification of clinical phenotypes among HF patients [ 24 ]. Nevertheless, a common limitation of these studies lies in their reliance on single-omics technology, which has not provided a comprehensive understanding of the distinctive proteomic and metabolomic patterns in HFpEF compared to those in HC. Given the complexities of biochemical regulation operating across various tiers, deriving meaningful insights from biological data sourced from a single-omics investigation can pose significant challenges. Hence, a holistic approach that integrates diverse omics datasets is instrumental in uncovering the fundamental biological interconnections and enhancing our grasp of the comprehensive biological processes at play in HFpEF.

In this study, we firstly analyzed HFpEF patients and healthy controls plasma samples to evaluate the metabolomics patterns. we found that all of the downregulated DEMs are phospholipids, suggests a potential disruption in cell membrane structure and function, signaling pathways, and inflammatory responses [ 25 ]. These disruptions can be due to altered lipid homeostasis, oxidative stress, inflammation, and other metabolic changes [ 26 , 27 ]. Then, the DEMs between HFpEF patients and HC were used for metabolic pathway analysis. pathways such as Tryptophan metabolism and tuberculosis were significantly altered, suggesting a complex interplay between metabolic disturbances and immune responses in the pathophysiology of HFpEF. It has been reported that inflammatory diseases are associated with dysbiosis- and host-related aberrant tryptophan metabolism [ 28 ]. Kynurenine circulates as a metabolite derived from the essential amino acid tryptophan. Masaaki Konishi et al. investigated that Kynurenine was higher in 76 HFpEF patients than in controls. Furthermore, in stable HF patients, an inverse relationship was observed between plasma kynurenine concentrations and both muscle strength and functional capacity, as well as hepatic and renal function [ 29 ]. Further research would be necessary to elucidate the exact mechanisms and to determine whether these metabolic changes are a cause or consequence of HFpEF.

Concurrently, an analysis was conducted on patients with HFpEF to discern proteomic variations in comparison to HC. This study identified 36 up-regulated and 10 down-regulated proteins in HFpEF patients compared to HC. We found that most of the DEPs particularly immunoglobulins, suggest an altered immune response in HFpEF patients. The significance of these findings could relate to the pathophysiology of HFpEF, where inflammation and immune responses are increasingly recognized as important factors [ 30 ]. The enrichment analysis of the KEGG pathway, focusing on significantly DEPs, has identified several prominent metabolic pathways. Notably, the P13K-Akt signaling pathway is the most significantly enriched pathway associated with HFpEF. Wouter Ouwerkerk’s PhD team identified The PI3K-Akt pathway as a significant association with all-cause mortality in HF [ 30 ]. Schulz E et al. have discussed the role of metabolic stress and the JNK pathway, which intersects with the PI3K-Akt pathway, in vascular function and injury [ 31 ]. One study also demonstrated that SGLT2 inhibitors touch on their potential effects on cardiac function and HFpEF, which may involve the PI3K-Akt pathway [ 32 ]. If SGLT2 inhibitors are found to modulate the PI3K-Akt pathway, either directly or indirectly through their metabolic effects, they might offer therapeutic benefits for patients with HFpEF. This could lead to new therapeutic strategies for HFpEF, a condition that has been challenging to treat effectively.

Subsequently, We next integrated the proteomics and metabolomics datasets to construct a comprehensive plasma profile panorama. Two pathways were significantly enriched in integrated multi-omics, including African trypanosomiasis and Tuberculosis pathway. IgM, IgG1, and Kynurenine which are involved in African trypanosomiasis pathway, IgM and IgG1 were significantly up-regulated in HFpEF compared to HC. Meanwhile, IgG and calcitriol are involved in Tuberculosis pathway, IgG is significantly up-regulated in HFpEF compared to HC. The enrichment analysis that highlighted the Tuberculosis and African trypanosomiasis pathways is particularly intriguing. The up-regulation of IgM and IgG1 in HFpEF patients suggests a heightened adaptive immune response [ 33 ]. It is known that chronic inflammation plays a role in the pathophysiology of HFpEF. The kynurenine pathway has also been linked to cardiovascular diseases, as it can lead to the production of metabolites that may have direct cardiovascular effects or modulate immune responses [ 34 ]. Calcitriol have been identified as risk factors for cardiovascular disease [ 35 ]. The association of calcitriol with HFpEF could reflect alterations in vitamin D metabolism, which has been suggested to be involved in the pathogenesis of heart failure. It has been reported that lower 25-hydroxyvitamin D (25(OH)D) levels were associated with reduced functional capacity in patients with diastolic dysfunction or HFpEF and were significantly predictive of an increased rate of cardiovascular hospitalizations [ 36 ].

Understanding the role of immune response and inflammation in HFpEF is crucial, as current treatment options are limited and largely focused on managing symptoms and comorbidities. These insights could lead to new strategies to modulate the immune response or metabolic pathways in HFpEF. It should be underscored that, although the results are indicative, additional investigation is required to confirm these pathways and elucidate their precise functions within the pathophysiological landscape of HFpEF. To the best of our knowledge, this represents the inaugural comprehensive multi-omic investigation that integrates untargeted proteomic and metabolomic datasets from HFpEF patients. It is imperative to acknowledge that the study was a single-center study and involved a limited number of participants. Consequently, to substantiate the findings presented herein, it is essential to undertake additional studies with larger cohorts. Moreover, supplementary experimental work is required to elucidate the mechanisms implicated in the pathogenesis of HFpEF, as suggested by the multi-omic analysis.

This study identified previously unreported proteomic and metabolomic alterations in HFpEF patients and HC based on the integrative metabolome and proteomics analysis of plasma samples. In conclusion, this study has unveiled a novel approach to elucidating the mechanism of HFpEF, integrating both proteomic and metabolomic analyses into the therapeutic exploration.

Proteomics analysis in patients with HFpEF compared to HC. PLS-DA score plot ( A ) and Cross-validation plot ( B ). The volcano plot ( C ) showed different proteins in HFpEF compared HC samples. ( D – F ) Categories of differentially expressed proteins according to GO. The three major categories of enriched GO functional classification: Biological Process ( D ), Cellular Component ( E ) and Molecular Function ( F ). ( G ) KEGG enrichment analysis of DEPs

Metabolomics analysis in patients with HFpEF compared to HC. Volcano plot ( A ) and heatmap ( B ) showed differently expressed metabolites in HFpEF compared to HC samples. ( C , D ) KEGG enrichment analysis of DEMs in positive ion mode ( C ) and negative ion mode ( D )

Integrated analysis of proteomics and metabolomics. ( A ) The hierarchical cluster analysis of the DEPs and DEMs. ( B , C ) Pathway enrichment analysis of DEPs and DEMs of positive ( B ) and negative ( C ) ion modes

Data availability

The sequencing datasets generated and analyzed during the current study are available in the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org/cgi/GetDataset? ID=PXD053164) via the iProX partner repository with the dataset identifier PXD053164. Other datasets analysed are available in this published article and the Supplementary information files.

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This study was supported by the Key R&D Program of Xinjiang Uygur Autonomous Region.

[Grant No. 2022B03023-4].

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Muyashaer Abudurexiti, Refukaiti Abuduhalike, Tuersunjiang Naman, Nuerdun Wupuer, Dongqin Duan, Mayire Keranmu & Ailiman Mahemuti

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AM participated in the review and editing.MA，RA performed experiments and analyzed date.TN analyzed date.MA wrote manuscript.NW, MK, DD Data curation, Writing- Original draft preparation. All authors read and approved the final manuscript.

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Abudurexiti, M., Abuduhalike, R., Naman, T. et al. Integrated proteomic and metabolomic profiling reveals novel insights on the inflammation and immune response in HFpEF. BMC Genomics 25 , 676 (2024). https://doi.org/10.1186/s12864-024-10575-w

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